U.S. patent application number 10/210548 was filed with the patent office on 2003-08-14 for herbal composition for angina pectoris, method to prepare same and uses thereof.
This patent application is currently assigned to Tianjin Tasly Pharmaceutical Co., Ltd., China. Invention is credited to Guo, Zhixin, Liu, Yan, Wu, Naifeng, Yan, Xijun, Ye, Zhengliang.
Application Number | 20030152651 10/210548 |
Document ID | / |
Family ID | 30443688 |
Filed Date | 2003-08-14 |
United States Patent
Application |
20030152651 |
Kind Code |
A1 |
Yan, Xijun ; et al. |
August 14, 2003 |
Herbal composition for angina pectoris, method to prepare same and
uses thereof
Abstract
This invention provides compositions comprising extracts of
Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneol. Said
compositions comprise notoginsenoside R.sub.1 and ginsenoside
R.sub.g1 which are active components for therapeutic applications.
This invention also provides a method of preparation of the said
compositions and a method of identification and determination of
the amount of individual effective components of said compositions.
Finally, this invention provides various uses of the
compositions.
Inventors: |
Yan, Xijun; (Tianjin,
CN) ; Wu, Naifeng; (Tianjin, CN) ; Guo,
Zhixin; (Tianjin, CN) ; Ye, Zhengliang;
(Tianjin, CN) ; Liu, Yan; (Tianjin, CN) |
Correspondence
Address: |
Albert Wai-Kit Chan
Law Offices of Albert Wai-Kit Chan, LLC
World Plaza, Suite 604
141-07 20th Avenue
Whitestone
NY
11357
US
|
Assignee: |
Tianjin Tasly Pharmaceutical Co.,
Ltd., China
|
Family ID: |
30443688 |
Appl. No.: |
10/210548 |
Filed: |
July 31, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10210548 |
Jul 31, 2002 |
|
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PCT/US01/49396 |
Dec 18, 2001 |
|
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60258057 |
Dec 22, 2000 |
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Current U.S.
Class: |
424/728 ;
424/746; 514/729 |
Current CPC
Class: |
A61P 39/00 20180101;
A61P 7/00 20180101; A61P 3/06 20180101; A61K 36/258 20130101; A61P
1/18 20180101; A61K 36/537 20130101; A61P 31/12 20180101; A61K
36/54 20130101; A61K 36/185 20130101; A61P 9/04 20180101; A61P
27/02 20180101; A61P 9/00 20180101; A61P 25/00 20180101; A61P 11/00
20180101; A61P 43/00 20180101; A61P 1/04 20180101; A61P 3/10
20180101; A61P 13/12 20180101; A61P 25/06 20180101; A61P 25/28
20180101; A61P 7/02 20180101; A61P 9/06 20180101; A61K 31/045
20130101; A61P 37/04 20180101; A61P 9/10 20180101; A61P 1/16
20180101; A61P 9/12 20180101; A61P 39/06 20180101; A61P 19/00
20180101; A61P 19/02 20180101; A61K 31/045 20130101; A61K 2300/00
20130101; A61K 36/185 20130101; A61K 2300/00 20130101; A61K 36/258
20130101; A61K 2300/00 20130101; A61K 36/537 20130101; A61K 2300/00
20130101; A61K 36/54 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/728 ;
424/746; 514/729 |
International
Class: |
A61K 035/78; A61K
031/045 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 21, 2000 |
TW |
90,132,075 |
Nov 9, 2001 |
CN |
01136155.7 |
Claims
What is claimed is:
1. A composition comprising extracts from the following herbal
materials in weight proportion:
139 Radix Salviae Miltorrhizae 48%.about.97%; Panax Notoginseng
2%.about.50%; and Borneol 0.2% .about.3%.
2. The composition of claim 1 wherein the weight proportions
are:
140 Radix Salviae Miltorrhizae 63.0%.about.94%; Panax Notoginseng
4.0%.about.35.0%; and Borneol 0.5%.about.2.0%.
3. The composition of claim 1 wherein the weight proportions
are:
141 Radix Salxriae Miltorrhizae 75.2%.about.90%; Panax Notoginseng
9%.about.23.5%; and Borneol 0.5%.about.1.3%.
4. The composition of claim 1 wherein the weight proportions
are:
142 Radix Salviae Miltorrhizae 82.87%; Panax Notoginseng 16.21%;
and Borneol 0.92%.
5. A pharmaceutical composition comprising the composition of claim
1, 2, 3 or 4 and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition for treating coronary heart disease
and angina pectoris comprising effective amount of extracts of
Radix Salviae Miltorrhizae, Panax Notoginseng and Borneol.
7. The composition of claim 6 wherein the Borneol is synthetic.
8. The composition of claim 6 comprising effective amount of the
composition of claim 1, 2, 3 or 4.
9. A method for treating a subject with coronary heart disease
comprising administering to the subject the pharmaceutical
composition of claim 6.
10. The method of claim 9 wherein the subject is a human.
11. A method for producing a composition of Radix Salviae
Miltorrhizae, Panax Notoginseng and Borneol comprising steps of: a.
obtaining appropriate amount of smashed Radix Salviae Miltorrhizae
and Panax Notoginseng; b. extracting the obtained Radix Salviae
Miltorrhizae, Panax Notoginseng in hot aqueous reflux; c. combining
the extracts to form a combined extract; d. concentrating the
combined extract to perform alcohol precipitation to obtain a
supernatant; e. eliminating the alcohol of the supernatant to
obtain a concentrated extract; f. mixing the concentrated extract
from step (e) with appropriate amount of borneol, thereby producing
the composition of Radix Salviae Miltorizae, Panax Notoginseng and
Borneol.
12. The method of claim 11, wherein the alcohol is an ethanol.
13. The method of claim 11 wherein step (b) the temperature is
between about 60 to about 100.degree. C.
14. The method of claim 11, wherein step (c), the extracts are
filtered before combination.
15. The method of claim 11 wherein step the ratio of the volume of
the concentrated extract to the weight of inputting herbal
materials being 1 liter: 0.7.about.1.3 kg.
16. The method of claim 11 wherein step (d) the final concentration
of ethanol is about 50-85%.
17. The method of claim 11 wherein step (d) the final ethanol
concentration is about 69-71%.
18. The method of claim 11 wherein step (d) the ethanol
precipitation is performed for 4-24 hours.
19. The method of claim 11 wherein step (d) the ethanol
precipitation for 8-12 hours.
20. The method of claim 11, wherein the supernatant obtained in
step (d) is filtered prior to the elimination of the alcohol.
21. The method of claim 11 wherein step (e) the concentrated
extract is to form a plaster of about 1.15-1.45 in relative
density.
22. The method of claim 11 wherein step (e) the concentrated
extract is to form a plaster of about 1.32-1.40 in relative
density.
23. The method of claim 11, wherein the borneol is synthetic.
24. The method of claim 11 further comprising packing the produced
composition into the form of a powder, syrup, tea, tincture,
injection, topical solution, capsule, pill, granule, tablet,
nebula, suppository microcapsule or other pharmaceutically
acceptable forms.
25. The method of claim 24 wherein the formation of the pill
comprising steps of: (i) mixing the concentrated extract plaster
from step (e), borneol and other ingredients; (ii) heating to melt
mixture and transfer it to a pill maker; (iii) pouring the melted
mixture into paraffin oil at a low temperature; (iv) removing the
paraffin oil; and (v) selecting the pills.
26. A method according to claim 25 wherein the other ingredient is
a pharmaceutically acceptable carrier.
27. A method according to claim 25 wherein the other ingredient is
Polyethylene glycol-6000 with a freezing point of about
53.about.58.quadrature..
28. A method according to claim 25 wherein the other ingredient is
Polyethylene glycol-6000 and the amount added is 2-6 times in
weight of the concentrated extract and borneol.
29. A method according to claim 25 wherein the Polyethylene
glycol-6000 added is 3 times in weight of the concentrated extract
and borneol.
30. A method according to claim 25 wherein the temperature for
melting the mixture is about 60-100 .quadrature..
31. A method according to claim 25 wherein the temperature for
melting the mixture is about 85-90 .quadrature..
32. A method according to claim 25 wherein the temperature of
paraffin oil is about 0-10 .quadrature..
33. A method according to claim 25 wherein the temperature of
paraffin oil is about 5-10.degree. C.
34. A method according to claim 25 wherein the temperature of
paraffin oil is about 7-8.degree. C.
35. A method according to claim 25 wherein the weight of the pills
are measured in about 5-50 mg/pill and 1.95-4.29 mm in
diameter.
36. A method according to claim 25 wherein the weight of the pills
are measured in 25.+-.15% mg/pill and 3.34.+-.15% mm in
diameter.
37. The composition produced by claims 11-35 or 36.
38. A pharmaceutical composition comprising the composition of
claim 37 and a pharmaceutically acceptable carrier.
39. The pharmaceutical composition of claim 38 wherein the Borneol
is synthetic.
40. The pharmaceutical composition of claim 38 for treating
coronary heart disease.
41. The pharmaceutical composition of claim 38 for treating angina
pectoris.
42. A method for increasing blood volume in coronary artery,
relaxing the smooth muscles of blood vessels, improving the
peripheral circulation, raising the oxygen content in veins, or
significantly improving the acute myocardial ischemia or myocardial
infarction in a subject comprising administering to the subject an
effective amount of the composition of claim 37.
43. A method for protecting the cells from damage by hypoxia,
anoxia, deoxygenation or re-oxygenation by contacting said cells
with effective amount of the composition of claim 37.
44. A method for protecting the cells from damage by hypoxia,
anoxia, deoxygenation or re-oxygenation in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
45. A method for protecting cells suffering from myocardial
ischemia by contacting said cells with effective amount of the
composition of claim 37.
46. A method for protecting cells suffering from myocardial
ischemia in a subject comprising administering to the subject an
effective amount of the composition of claim 37.
47. A method for improving micro-circulation in a subject
comprising administering to the subject an effective amount of the
composition of claim 37.
48. A method for preventing arrhythmia in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
49. A method for preventing platelets aggregation, thrombosis and
dissolve fibrin in a subject comprising administering to the
subject an effective amount of the composition of claim 37.
50. A method for lowering blood viscosity, adjusting the blood
cholesterol or preventing atherosclerosis in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
51. A method for raising the tolerance to hypoxia, anoxia,
preventing the oxidation of lipoprotein or removing the harmful
free radicals in a subject comprising administering to the subject
an effective amount of the composition of claim 37.
52. A method for lowering plasma ET content, significantly improve
the liver, kidneys and pancreas functions in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
53. A method for preventing the occurrence or development of blood
vessel or nerve diseases in a subject comprising administering to
the subject an effective amount of the composition of claim 37.
54. A method for enhancing the immune system in a subject
comprising administering to the subject an effective amount of the
composition of claim 37.
55. A method for regulating the vascular nervous balance in a
subject comprising administering to the subject an effective amount
of the composition of claim 37.
56. A method for preventing and treatment cardiovascular and
cerebrovascular diseases, kidney disease, liver disease, pneumonia,
lung or heart disease, pancreatitis, diabetes, vertebral disease,
optic vessels disease, optic nerves disease, eccentric headache,
chronic stomachitis, dizziness, bone diseases, altitude diseases,
common elderly diseases in a subject comprising administering to
the subject an effective amount of the composition of claim 37.
57. A method for treating stable angina pectoris, unstable angina
pectoris, aged angina pectoris, non-symptomatic myocardial
ischemia, different types of coronary heart diseases or angina
pectoris diseases in a subject comprising administering to the
subject an effective amount of the composition of claim 37.
58. A method for treating arrhythmia, enlargement of left
ventricle, myocarditis, myocardial infarction or cerebral
infraction in a subject comprising administering to the subject an
effective amount of the composition of claim 37.
59. A method for rapidly relieving coronary heart disease or angina
pectoris in 3-10 minutes when it is taken sublingually in a subject
comprising administering to the subject an effective amount of the
composition of claim 37.
60. A method for treating hyperlipidaemia, high blood viscosity
syndrome or high blood pressure in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
61. A method for treating coronary heart disease and high blood
pressure, coronary heart disease and hyperlipidaemia, coronary
heart disease, enlargement of left ventricles and coronary heart
disease or arrhythmia in a subject comprising administering to the
subject an effective amount of the composition of claim 37.
62. A method for treating diseases caused by micro-circulation
disorder in a subject comprising administering to the subject an
effective amount of the composition of claim 37.
63. A method for treating stroke, cerebral infarction, cerebral
bleeding and other cerebral diseases in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
64. A method for treating hepatitis B, chronic liver fibrosis,
liver fibrosis, active liver cirrosis, liver cirrosis in
compensation period and other related diseases in a subject
comprising administering to the subject an effective amount of the
composition of claim 37.
65. A method for treating kidney syndrome and its conjunctive
diseases in a subject comprising administering to the subject an
effective amount of the composition of claim 37.
66. A method for treating diabetes or its conjunctive diseases in a
subject comprising administering to the subject an effective amount
of the composition of claim 37.
67. A method for treating cyanosis-typed optic vessels diseases
such as venal blockage in retina, central optic artery blockage in
retina, high blood pressure optic atherosclerosis in retina,
diabetic retinopathy, cento-neuropathy, cento-osmotic neuropathy,
ischemic neuropathy, optic neuritis or optic nervous dystrophy in a
subject comprising administering to the subject an effective amount
of the composition of claim 37.
68. A method for treating dizziness caused by cerebral-arterial
ischemia, Meniere's disease, high blood pressure, coronary heart
disease in a subject comprising administering to the subject an
effective amount of the composition of claim 37.
69. A method for enhancing the immune system in a subject
comprising administering to the subject an effective amount of the
composition of claim 37.
70. A method for regulating the vascular nervous balance in a
subject comprising administering to the subject an effective amount
of the composition of claim 37.
71. A method for treating detrimental death of epicondylus
medialis, femoral end necrosis, twisted joint, ligament damage,
fracture and proliferation of bone cells in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
72. A method for treating bronchitis in children in a subject
comprising administering to the subject an effective amount of the
composition of claim 37.
73. A method for treating hypoxia or anoxia in a subject comprising
administering to the subject an effective amount of the composition
of claim 37.
74. A method for treating Alzhemier's Disease in a subject
comprising administering to the subject an effective amount of the
composition of claim 37.
Description
[0001] This application is a continuation-in-part of International
Patent Application No. PCT/US01/49396, filed Dec. 18, 2001 which
claims benefit of U.S. Serial No. 60/258,057, filed Dec. 22, 2000,
the content of which are incorporated here into this
application.
[0002] Throughout this application, various publications are
referenced and the disclosures of these publications are hereby
incorporated by reference into this application in order to more
fully describe the state of the art as known to the skilled therein
as of the date of the invention described and claimed herein.
BACKGROUND OF THE INVENTION
[0003] Chronic stable angina pectoris is due to transit myocardial
ischemia. Aspirin, nitrates, beta-adrenoceptor blocking drugs, and
calcium channel blocking drugs used alone or in combination with
one another are the commonly used drugs for angina pectoris.
[0004] Aspirin as an antithrombotic agent is a symptomatic
treatment for chronic stable angina pectoris.
[0005] Nitrates are used to treat an anginal episode and can be
successfully used in prophylaxis by patients with predictable
symptoms. With all nitrates, troublesome headache can prevent their
use in certain susceptible individuals.
[0006] Beta-adrenoceptor blocking drugs, although established as a
cornerstone in the treatment of angina, are specifically
contraindicated in patients with obstructive airways diseases and
severe ventricular dysfunction, and relatively contraindicated in
diabetes and in those with peripheral vascular disease, bradycardia
or heart block.
[0007] Calcium antagonists are certainly effective in angina,
achieving their effects by smooth muscle relaxation in the coronary
arteries and peripheral circulation, increasing myocardial supply
and reducing myocardial work.
[0008] Although there is progress in drug combination therapy in
angina, which most patients begin treatment with nitrates and a
beta-adrenoceptor blocking drug or a calcium antagonist, there is a
need of drug for chronic stable angina pectoris which is very
effective, can be taken for a long period of time and has very low
toxicity.
[0009] In view of the problems of relating to the above mentioned
drugs, notable efforts have been made to apply herbal Medicine as
an alternative to the standard treatment of chronic stable angina
pectoris. Traditional Chinese Medicine (TCM) has contributed much
in this respect.
[0010] U.S. Pat. No. 5,288,485 and 5,433,957 refer to an extract
from Hypericum erectum thunb for curing or preventing diseases
caused by disorder in blood circulation such as angina
pectoris.
[0011] U.S. Pat. No. 5,776,463 refers to an oral pharmaceutical
composition containing petals of borage or extract of borage petals
for the prevention and treatment of stress which is associated with
circulatory heart diseases including angina.
[0012] In addition to Hypericum erectum thunb and borage petals,
many other herbal plants have also been used to treat angina. One
such plant is Valeriana officinalis latifolia. Yang G Y et al
(1994) Reported that 82 patients with angina pectoris had been
treated with Valeriana officinalis latifolia, among whom ST-T
ischemic changes appeared on ECG in 50 cases before treatment. Its
total effective rate for simple angina (without detectable ischemic
findings) was 87.80%; the angina with ischemic findings, 88.00%. In
addition, it was discovered that Valeriana officinalis latifolia
could lower plasma lipids as well. No toxic actions to liver,
kidney, and hemopoietic tissue, have been found.(1) Wu Y (1990)
reported that in a setting of 267 patients with angina pectoris,
93.3% of the patients treated with xintongkang capsule was
effective.
[0013] Another herbal preparation called Shenshao tongguan pian was
used in treating angina pectoris. In 1990, Hu J X et al. Reported
that the Shenshao tongguan pian is composed chiefly of saponin from
the stem and leaves of Ginseng and Radix Paeoniae alba, etc. The
total effective rate for treating angina pectoris was 94.71%. And
the ECG improvement rate was 63.38%. In addition, laboratory
examination also revealed that Shenshao tongguan pian could promote
the left ventricular output, lower the blood viscosity and inhibit
the aggregation of blood platelet. Both acute and chronic toxicity
tests showed that Shenshao tongguan pian has no toxicity or side
effects.
[0014] Kuo-guan granule is another herbal preparation for angina
pectoris. Li Y et al. (1990) reported that the changes of the
plasma zinc, copper and erythrocyte glutathione peroxidase were
measured by atomic absorption spectrometry and DTNB color
development in 31 patients suffering from coronary heart disease
with angina pectoris before and after taking Kuo-Guan granule for
one month. The results indicated that the plasma zinc and
erythrocyte glutathione peroxidase were lower and copper was higher
in the patients than the normal control group before treatment
(P<0.01), the plasma zinc and erythrocyte glutathione peroxidase
increased and copper decreased after treatment (P <0.01). These
suggest that therapeutic mechanism of Kuo-Guan granule for coronary
heart disease with angina pectoris may relate to its regulation on
trace elements disturbance in body.
[0015] Saponin of Tribulus terrestris was another herbal
composition for treating angina pectoris.
[0016] Fufang Danshen Pian is a folk prescription of Dan Shen
Tablet which indicate for treating chronic stable angina pectoris
due to coronary artery ischemia and has been officially listed in
the editions of Chinese Pharmacopoeia since 1977 and applied to
clinical use for decades.
[0017] Fufang Danshen Pian contains multiple active extracts of
botanical including Danshen (Radix Salviae Miltiorrhizae), and
Sanchi (Radix Notoginseng). Both of the botanical were first
documented in Shen Nong Ben Cao Jing (Shen-nong's Herbal
Pharmacopoeia) completed in 200. Fufang Danshen Pian also contains
synthetic borneol, a version of a natural borneol (Bingpian).
Natural borneol was first documented in Tang Ben Cao (Herbal
Pharmacopoeia of the Tang Dynasty) compiled around 659.
[0018] Li Cheng-zhu et al (1979) reported in (Acta Acad Med Prim
Shanghai) on an experimental study of thrombotic inhibition effect
of Radix Silviae Miltiorrhizae. Effects on in vi tro thrombosis,
functions of platelet and coagulation, fibrinolysis were observed
in rabbits. After injection of Radix Silviae Miltiorrhizae, 3 links
were found to play an important role in inhibition of in vitro
thrombosis: (1) inhibition of platelet function; (2) inhibition of
coagulation function; and (3) promote fibrinolysis. Of which, the
former two mechanisms function more intensely. The results conform
to those in the treatment of thrombotic diseases, especially
arterial thrombotic diseases.
[0019] Chiang W T et al (1982) reported in (Acta Acad Med Prim
Shanghai) the effects of "Danshensu" and other two water-soluble
components of Salvia miltiorrhiza on dog ischemic myocardium and
isolated pig coronary artery. The effect of 3 new water-soluble
components i.e. Danshensu (DS-182, D(+)-3,4-dihydroxyphenyl lactic
acid), protocathu-aldehyde (PCAD) and an impure diterpene acid
(DS-187) isolated from Salvia miltiorrhiza bunge, were compared
with those of dipyridamole. Results revealed (1) in mice, DS-182
gave significant protection against hypoxia, whereas PCAD was
ineffective; (2) DS-182 could nullify the pituitrin-induced
electrocardiographic ischemic ST-T elevation but had no influence
on the reduced heart rate. DS-187, PCAD and dipyridamole only
showed incomplete protection; (3) in the acutely infarcted dog
model prepared by ligation of the anterior descending branch of the
left coronary artery, the benefits achieved by intravenous
injection of DS-182 proved superior to DS-187 and PCAD in respect
to the left ventricular function, left ventricular peak systolic
pressure (LVPSP) and left ventricular end diastolic pressure
(LVEDP). PCAD, on the contrary, produced adverse effects on LVPSP
and LVEDP. Intravenously administered dipyridamole, though it did
not change LVEDP, suppressed LVPSP significantly with marked
hypotensive effect. All these components of Salvia and dipyridamole
significantly reduced the ultimate myocardial infarct size (N-BT
assessment); Ds-182 was most effective, dipyridamole and DS-187 the
next, while PCAD the least; (4) in the isolated perfused pig
coronary artery preparation, DS-182 significantly reduced the
resistance of the coronary vessel, whereas either DS-187, PCAD or
sodium Tanshinone II-A sulfonate (DS-201), another component of
Salvia, increased it. The constrictory action of morphine and
propranolol on the isolated coronary artery preparation was
antagonized by the prior administration of DS-182. All of these
suggested that Danshensu might be the main active principle of
Salvia miltiorrhiza in treating ischemic heart disease and that its
concomitant use with propranolol or morphine would be
beneficial.
[0020] Li Cheng-zhu et al (1983) reported in (Chin J Integr Med)
the anti-coagulation effect of Radix Silviae Miltiorrhizae.
Danshensu is a water-soluble monomer extracted from Radix Silviae
Miltiorrhizae. It is also the main ingredient of commercially sold
Injection Radix Silviae Miltiorrhizae. The present study proved
that Danshensu inhibits thrombosis in vitro, aggregation of
platelet (induced by ADP), and internal and external coagulation
systems; diminishes the number of platelets and promotes the
degradation of fibrin or fibrinogen. The effects peaked 30 minutes
after a single injection of 20 mg/kg in rabbits, lasted for 1 hour,
and recovered gradually. 4.5 hours after injection, all recovered
to normal but thrombosis test in vitro. Chen Zhanghua (1987)
reported in Acta Acad Med Prim Shanghai on effects of "Danshensu"
on experimental microcirculatory disturbances and plasm lactic acid
concentrations. Natural Danshensu is a water soluble monomer
extracted from Radix Salviae Miltiorrhizae (RSM). Microcirculatory
disturbances in rabbits were induced by intravenous injection of
high molecular weight dextran. Natural Danshensu (dosage 4-6 mg/kg)
markedly increased the number of capillary vessels in the bulbar
conjunctiva, and also decreased the concentration of plasm lactic
acid in the rabbits. Mesenteric microcirculatory disorders were
produced by local noradrenaline (4 g) drip in mice. Natural
Danshensu dilated the arteries and accelerated the speed of blood
flow, thus eliminating microcirculatory blood stasis. In our
experiments, effects of synthetic Danshensu were observed
concomitantly. The results showed that there was no significant
difference between natural and synthetic Danshensu in relieving
microcirculatory disturbances.
[0021] Sun Xi-ming et al (1991) reported a new pharmacological
action of an extract of Danshen (Salvia miltiorrhiza). The paper
reports that an extract of Danshen (Salvia miltiorrhiza) which
contains the sodium salts of D(+)-(3,4-dihydroxy phenyl) lactic
acid was found to possess a new pharmacological action of
decreasing the biosynthesis of cholesterol in cells and
anti-lipoprotein oxidation, by cell cultural studies. When compared
with the control, its electrophoretic migration rate was markedly
lowered and MDA content and cytotoxicity decreased obviously. These
results indicated that salts of D(+)-(3,4-dihydroxy phenyl) lactic
acid may be effective in the prevention and treatment of
atherosclerosis.
[0022] Zheng Ruo-xuan et al (1992) reported in (Chin J Integr Med)
the preservation effect of Radix Silviae Miltiorrhizae on
myocardial ischemia induced by coronary ligation in mice. Obvious
preservation effect on acute myocardial ischemia in mice by
coronary ligation could be obtained after i.p. water-extract of
Radix Silviae Miltiorrhizae (5 g crude drug/kg). S-T segment
elevation on ECG due to myocardial ischemia in the treatment group
was much lower, ischemic size of the left ventricle was smaller and
the survival rate was higher when compared with the control.
[0023] Wu Yao-zhong et al (1995) reported in (Acta Nanjing Univ
Trad Chin Mater Med) on effects of Radix Silviae Miltiorrhizae in
promoting blood circulation by removing blood stasis.
Pharmacological research of Radix Silviae Miltiorrhizae is common.
However, rheological studies on Radix Silviae Miltiorrhizae by
assessing PGI2, ET, and TXA2 produced by platelet are seldom.
Influence of Radix Silviae Miltiorrhizae on thrombosis, changes of
PT, KPTT, FG, ESR and HCT, and aggregation of platelet in rabbits
are evaluated in the present study. Conclusions are that Radix
Silviae Miltiorrhizae reduces the synthesis of TXA2 and decreases
the effects of enhancement of platelet aggregation and
thrombosis.
[0024] Shi Linet al (1990) reported in (Acta Pharmcol Sin) on the
effects of total saponins of Panax Notoginseng on increasing
PGI.sub.2 in carotid artery and decreasing TXA2 in blood platelet.
Total saponins of Panax notoginseng (PNS) were given orally 100
mg/(kg.day) to rabbit for 8 wk. Aortic atherosclerotic plaque
formation was restrained as compared that of to the control group.
Radioimmunoassay was used to investigate the effects of PNS on the
contents of prostacyclin in carotid artery and thromboxane A2 in
rats' blood platelet. Oral administration of PNS 25, 50, 100
mg/(kg.day) for 10 days caused an increase of prostacyclin in
carotid artery and a decrease of thromboxane A2 in blood platelet
as compared with the control group. These results showed that the
anti-atherosclerotic action of PNS may be a result of the
correction of the imbalance between prostacyclin and thromboxane
A2.
[0025] Li Xing et al (1990) reported in (Acta Pharmacol Sin) the
Protective effects of Panax Notoginseng saponin on experimental
myocardial injury induced by ischemia and reperfusion in rats.
Effects of total saponin of Panax Notoginseng (PNS) and purified
ginsenoids R.sub.b1 and Rg.sub.1 from PNS on myocardial injury
induced by cardiac ischemia and reperfusion were studied using rat
hearts in situ and in vitro. In pentobarbital-anesthetized rats,
PNS pretreatment (100 and 200 mg/kg) provided significant reduction
in myocardial infarcted size after left descending coronary artery
ligation (40 min) and reperfusion (120 min) in comparison with the
control. PNS 12.5 and 25 mg/L, R.sub.b1 10 mg/L and R.sub.g1 110
mg/L significantly decreased cardiac CPK release, attenuated
myocardial Ca.sup.++ accumulation, reduced malondialdehyde (MDA)
production and prevented reduction of superoxide dismutase (SOD)
activity in comparison with the control in perfused isolated rat,
hearts with global ischemia (40 min) and reperfusion (15 min) The
results showed that PNS, R.sub.b1 and R.sub.g1 prevented cardiac
ischemia and the action was considered to be related to the
inhibition of lipid peroxidation.
[0026] Huang Cong et al (1991) reported in (Chin Bull Pharmacol)
the effects of Panax Notoginseng Saponin on myocardial ischemia and
reperfusion injury in conscious rabbits. The effects of Panax
Notoginseng saponin (PNGS) on myocardial ischemia and reperfusion
injury in conscious rabbits were studied with observation of
changes in electrocardiogram (ECG), the activities of creatine
phosphokinase (CPK) and lactate dehydrogenase (LD) and the size of
ischemic area. PNGS at the dose of 50 mg/kg and 100 mg/kg
significantly reduced the size of myocardial ischemic area. These
results suggested that PNGS have the protective effects on
myocardial ischemia and reperfusion injury.
[0027] Mo Qi-xian et al (1987) reported in (Propriet Trad Chin Med
Res) the dynamics of .sup.3H-Borneol. In order to highlight the
mechanism of inducing resuscitation of Borneol aromaticity,
dynamics of 3H-Borneol were conducted by intraveneous injection and
oral administration. The results revealed that the half-life time
was 2.8 min after a single intraveneous injection of 3H-Borneol. It
suggested that the drug distributed rapidly to the relevent organs
and tissues after administration and produced prompt effect. In
vivo distribution concentrated on organs and tissues which are
abundant in blood flow, such as heart, lung, liver, kidney and
brain, etc. This provided clinical application certain theoratical
basis. Since the diminishing half-lifetime was 5.3 hours after oral
administration of the drug, this suggested that oral Borneol could
not lead to accumulation, but poor bioavail-ability. Further
studies should be taken to discusse the relationship with drug dose
and dosage form.
[0028] Chen Tie-feng et al (1990) reported in (Acta Pharmacol Sin)
the enhancement of absorption of tetramethylpyrazine by synthetic
borneol. Sprague-Dawley rats were given ig tetramethylpyrazine
phosphate (TMP) 5 mg/kg with or without previous borneol 5 mg/kg.
The plasm TMP concentrations were analysed by GC method, and the
data were treated by NONLIN program. The Cmax were 931 and 562
ng/ml, respectively, (p<0.01); while the AUC were 68849 and
37174, respectively, (P<0.05). It is suggested that the borneol
enhances the absorption of the TMP but not in elimination. Xu Wei
et al (1995) reported in (Pharmacol Chin Med Clin) the effect of
menthol and borneol on the distribution of sulfadiazine sodium and
Evan's blue in the rat and mouse brain. Menthol (1.5 g/kg, ig) and
Borneol (1.5 g/kg) prolonged the sulfadiazine sodium distribution
half-life t.sub.1/2 in rats. The above dosage of menthol and
borneol given orally also increased the concentration of
sulfadiazine sodium in the rat brain. Menthol (ig 0.5 g/kg for 3
days) and borneol (ig 0.5 g/kg for 3 days) promoted the
concentration of Evan's blue in the mouse brain, but the value of
concentration was significantly lower than that of the mice
suffering from the ischemia-reperfusion injury. The results
suggested that the menthol and borneol could enhanced the
sulfadiazine sodium transfer in brain-blood barrier with no damage
to brain-blood barier.
[0029] In the United States, coronary atherosclerotic heart disease
is the commonest cause of cardiovascular disability and death.
[0030] Atherosclerosis is an arterial disorder characterized by
yellowish plaques of cholesterol, lipids, and cellular debris in
the inner layers of the walls of large and medium-size arteries.
The condition begins as a fatty streak and gradually builds to a
fibrous plaque or atheromatous lesion. The blood vessel walls
become thick, fibrotic, and calcified. The artery lumen narrows.
Many atherosclerotic plaques remain stable or progress gradually.
Others may rupture resulting in hemorrhage, platelet activation,
and thus intravascular thrombosis. Coronary thrombosis causes
partial or complete vessel occlusion, impairs blood flow, thus
leads to unstable angina or myocardial infarction. Alternately, the
ruptured plaques may become restabilized, often more severe
stenosis.
[0031] Exercise and mental stresses increase myocardial oxygen
demand. Under normal physiological condition, increased myocardial
oxygen demand is met by the arterioles dilating thus increasing
blood flow. In the presence of atherosclerosis, the arterioles may
dilate maximally to meet basic demand. Such dilated arterioles may
be unable to meet the increased myocardial oxygen demand. When
oxygen demand exceeds oxygen supply, the ischemia of myocardium
occurs. Alternately, severe vessel occlusions may limit blood flow
thus cause myocardial ischemia. Clinical manifestations of
transient myocardial ischemia is angina pectoris which is a
paroxysmal thoracic pain, frequently spread to the arms,
particularly to the left arm, with or without accompanied by a
feeling of suffocating and impending death.
[0032] Angina pectoris is subdivided in to two: stable and
unstable. Stable angina pectoris is caused by the increased
myocardial oxygen demand in most cases. Stable angina thus attacks
in the predictable frequency and duration upon provocation which
increases myocardial oxygen requirements such as exercise, mental
stress, etc. In contrast, unstable angina pectoris attacks without
provocation and usually caused by decreased oxygen supply to
myocardium. Plaque disruption, platelet plugging, and coronary
thrombosis decrease oxygen supply to myocardium.
[0033] Angina pectoris is treated with various drugs, surgical
procedure, coronary artery bypass graft, balloon-angioplasty, stent
placement, etc. Therapy for stable angina pectoris is primarily to
minimize myocardial oxygen demand as well as a preventive measure.
Therapy for the acute syndrome unstable angina pectoris is
primarily to inhibit platelet activation and thrombolysis.
[0034] Current therapeutic agents for chronic stable angina
pectoris are nitroglycerine, other nitrates, calcium channel
blockers, and beta-adrenergic receptor blockers. These drugs,
administered alone or in combination with other drugs, alleviate or
prevent rather than cure angina.
[0035] When angina attacks, nitroglycerine is administered
sublingually to alleviate symptoms. Nitroglycerine is also applied
to prevent anginal attacks caused by exertion and stress. Nitrates
are applied to prevent angina attacks. Nitroglycerine and nitrates
mediate their effect primarily by relaxing vascular smooth muscle,
reducing myocardial activity, and thus reducing myocardial oxygen
demand. The side effects are throbbing headache, dizziness,
weakness, orthostatic hypotension, tachycardia, etc.
[0036] Beta-adrenergic receptor blockers such as propranolol are
applied to prevent angina pectoris by reducing myocardial oxygen
requirements during exertion and stress. The major
contraindications are bronchospastic disease, bradyarrhythmias, and
overt heart failure. In individuals with asthma and other forms of
airway obstruction, beta-blockers may worsen their condition.
[0037] Calcium antagonists are applied to prevent angina pectoris
by reducing the oxygen demand of myocardium. Myocardium is
dependent on calcium influx for normal functions. By inhibiting
calcium influx, calcium antagonists may relax smooth muscle of the
blood vessel, decrease myocardium activity, reduce oxygen demand by
myocardium, and thus prevent angina pectoris. Calcium antagonists
have adverse side effects. The mild side effects are flushing,
edema, dizziness, nausea, etc. Excessive inhibition of calcium
influx to myocardium may cause severe side effects such as cardiac
arrest, bradycardia, artrioventricular block, congestive heart
failure, etc. Combined with beta-adrenergic drugs, the side effects
of calcium antagonists are often augmented.
[0038] In China, Panax Notoginseng and Radix Salviae Miltorrhizae
have been used for treating cardiovascular disease since 200 AD
(Shen-nong's Herbal Pharmacopoeia). Panax Notoginseng has been used
for treating angina pectoris. Radix Salviae Miltiorrhizae has been
used for promoting blood circulation and dispersing blood stasis.
Numerous preclinical and clinical studies demonstrate the efficacy
and safety of Panax Notoginseng and Radix Salviae
Miltiorrhizae.
[0039] Traditional Chinese medicine is the mixture of several herbs
requiring decoction. A modified form of Chinese medicine for
treating coronary heart disease is Dan Shen tablet. Dan Shen tablet
is a large unctuous ball, often as large as 1cM in diameter. Dan
Shen tablets are made of the extract of Radix Salviae
Miltiorrhizae, powder of Panax Notoginseng and synthetic borneol,
have been listed in the Chinese Pharmacopoeia since 1977, and have
been used to treat cardiovascular disease for decades.
[0040] The disclosed Danshen pill (DSP) or called cardiotonic pill
is a new generation Chinese medicine for coronary heart diseases.
Chinese medicine consists of various herbs which vary from
prescription to prescription in regard to the type of herbs as well
as the proportion of herbs. To control the quality, DSP is
manufactured with the standarized formula. The therapeutic
components of DSP are the water-soluble extracts of Radix Salviae
Miltiorrhizae 10-30% and sometimes, approximately 20%, the
water-soluble extracts of Panax Notoginseng (2-6%), and borneol
(1-3%). Furthermore, to alleviate angina quickly, DSP been
manufactured as a small pill which can be dissolved immediately
upon sublingual administration, delivered to myocardium quickly,
and thus alleviate angina fast.
[0041] DSP has been proven to be nontoxic and effective for the
prevention and treatment of cardiovascular disease caused by
coronary artery ischemia in preclinical and clinical studies.
Furthermore, the superior efficacy of DSP to Dan Shen tablets for
treating coronary arterial disease has been demonstrated in
preclinical as well as in clinical studies.
[0042] DSP has been listed in the Supplement Edition of Chinese
Pharmacopoeia since 1998, approved by the Chinese Ministry of
Health, marketed as a drug in China since 1993, and used by more
than five million people.
SUMMARY OF THE INVENTION
[0043] The disclosed Dan Shen Pill (DSP) is a new generation of
Chinese medicine for treating coronary heart disease manufactured
with the standarized formula. DSP comprises the standarized amount
of the extracts of Panax Notoginseng, the extracts of Radix Salviae
Miltorrhizae, and Borneol.
[0044] Panax Notoginseng is included to alleviate and to prevent
angina. Radix Salviae Miltorrhizae is included to inhibit platelet
activation, to prevent coronary thrombosis, and thus to promote
blood circulation. Borneol is included for the effective delivery
of therapeutic components to myocardium.
[0045] DSP is manufactured as a small pill, approximately 25 mg,
which can be dissolved immediately upon sublingual administration
and thus to mediate its therapeutic effects quickly. The efficacy
of DSP alleviating and preventing angina has been proven in
preclinical and clinical studies.
[0046] This invention discloses a dropping machine by which DSP or
other small size pills can be manufactured.
[0047] This invention discloses a method of controlling the quality
of medicaments by identifying and quantitating the therapeutic
components in medicaments applying analytical techniques, such as
thin layer chromatography, high performance liquid chromatography,
etc.
DETAILED DESCRIPTION OF THE FIGURES
[0048] FIG. 1. Batch No. 19990806
[0049] FIG. 2. Batch No. 19990815
[0050] FIG. 3. Batch No. 19990823
[0051] The position of fingerprint peaks: Group I consisting of
peak 1 and 2 (retention time ranging from 7 to 15 min); Group It
consisting of peak 3 and 4 (retention time ranging from 15 to 20
min); Group III consisting of peak 5, 6, 7 and 8 (retention time
ranging from 20 to 40 min). From whole sight, the abundance of
peaks in the group I is largest, and that the height of peak 1 is
close to the peak 2. The peaks in the group II stand side by side,
posses same heights almost and the abundance is very small. The
group III is composed of 4 peaks, and their height increase step by
step. These three groups compose the representative fingerprint of
Compound Danshen Dripping pills.
DETAILED DESCRIPTION OF THE INVENTION
[0052] This invention provides a method for identifying Sodium
Danshensu and protocatechuic aldehyde in a herbal composition
capable of treating chronic stable angina pectoris by thin layer
chromatography comprising the steps of (a) preparing the assay: (i)
dissolvinjg an appropriate amount of the said composition in
methanol, (ii) contacting an appropriate amount of the solution
onto a silicon G gel plate containing 0.5% CMC-Na, (iii) developing
the plate with a developing solution comsisting of Chloroform,
acetone and methane acid in the ratio of 10:4:1.6, (iv) drying and
fumigating the plate with ammonia and laying the plate up for 15
minutes, (v) checking the plate under ultraviolet light, the spot
representing the said composition should be at the corresponding
position of the standards and show the same color; and (b) using
Sodium Danshensu and protocatechuic aldehyde as the standards.
[0053] This invention also provides a method for identifying
gypenoside of an herbal composition capable of treating chronic
stable angina pectoris by thin layer chromatography comprising the
steps of (a) preparing the assay: (i) dissolving an appropriate
amount of the said composition in ammonia solvent, (ii) applying
the dissolved composition into the macroporous adsorption resin
column; the speed is 0.5/minute, (iii) washing the macroporous
adsorption resin column and eluting the macroporous adsorption
resin column with methanol, (iv) collecting the eluant, (v)
contacting the eluant onto a silicon G gel plate containing 0.5%
CMC-Na, (vi) developing the plate with 10 ml developing solution,
(vii) after being dried and sprayed with 10% ethanol sulfate, the
plate is baked at 105.degree. C. for several minutes, (viii)
checking the plate under normal light, the spot representing the
said composition should be at the corresponding position of the
standards and show the same color; and (b) using total gypenoside,
Saponin R1 and ginsenoside R.sub.g1 as the standards.
[0054] This invention further provides a method for identifying a
herbal composition capable of treating chronic stable angina
pectoris comprising the steps of (a) preparing the assay: (i)
dissolving a suitable amount of Dan Shen Dropping Pellet
composition in internal standard para-aminobenzonic acid solvent,
(ii) diluting the solution with methanol and centrifuging, (iii)
collecting the supernatant; (b) using Danshensu and protocatechuic
aldehyde as the standards; (c) performing the HPLC assay; and (d)
calculating according to the internal standard method.
[0055] In addition, this invention provides a composition
comprising the product that when subjected to the above method
produces 8 peaks as shown in FIG. 1 and produces a fingerprint as
tabulated here.
1 Relative Retention Retention Appearance Area Ratio Peak No. Time
Time Probability Area Area Ratio Range 1 8.289 0.672 100% 1034.276
0.572 0.572 .+-. 0.096 2 12.343 1.000 100% 1817.065 1.000 1.000
.+-. 0.000 3 17.493 1.417 100% 376.547 0.208 0.208 .+-. 0.040 4
18.664 1.512 100% 328.011 0.181 0.181 .+-. 0.059 5 24.883 2.016
100% 486.626 0.267 0.267 .+-. 0.097 6 27.586 2.235 100% 525.432
0.289 0.289 .+-. 0.052 7 29.714 2.407 100% 940.963 0.516 0.516 .+-.
0.125 8 34.030 2.757 100% 1547.495 0.850 0.850 .+-. 0.163
[0056] The invention provides an herbal composition capable of
treating chronic stable angina pectoris comprising about 0.14 to
about 0.18 mg Danshensu per pill. This invention also provided the
above composition comprising more than 12.12 .mu.g sanchinoside R1
per pill and more than 56.26 .mu.g ginsenoside Rg1 per pill. This
invention further provides the above composition comprising about
10-30% water soluble phenolic acid components from Radix Salviae
Miltorrhizae, 2-6% extract of saponin from Radix Notoginseng, and
about 1-3% borneol with pharmaceutically suitable carriers.
[0057] The present invention provides a method for obtaining an
herbal composition capable of treating chronic stable angina
pectoris comprising the steps of (a) Applying Radix Salviae
Miltorrhizae into the multifunction extraction tank; add water
until it is 15-20 cm over the herb (about 5-7 times the quantity of
the herb); heat them up to boiling with steam, while the inside air
pressure should be controlled in between 0.04-0.06 mPa; keeping the
tank in boiling condition. Boiling twice, first for 2 hours and
then for 1.5 hours. The extract is filtrated at the bottom of the
extraction tank through a 100-mesh net into a stock tank, the
remaining is discarded; (b) Transferring the solution from the
stock tank into a vacuum tank. The steam is controlled at below
0.05 mPa. In the mean time, adjust the vacuum to 0.076.about.-0.088
mPa to keep the tank in boiling condition. The solution is
concentrated to about the solution volume (Liter) to the herb
quantity (kilogram) in the ratio of 1:1; (c) Filtering and adding
95% ethanol to the solution with slow stirring until the ethanol
concentration of the solution reaches 70% measured by ethanol
gravimeter for 24 hours; (d) Opening the tank, transferring the
supernate of the ethanol precipitated solution through 100 mesh net
into a vacuum concentration tank, adjusting the air input to
0.04-0.06 mPa and the vacuum to -0.076.about.-0.088 mPa to keep the
tank boiling but bumping and recovering the ethanol to the herb
solution to about the solution volume (Liter) to the herb quantity
(kilogram) in the ratio of 1:1; (e) Loading the solution from step
(d) into the pre-treated polyamide chromatography with the loading
volume 5 ml/gram polyamide and washing the column with 3 volume
times water, eluting the column with 5-10 times 95% ethanol; and
(f) Recovering the ethanol as in the step d to concentrate the
eluant to the density of 1.33-1.35.
[0058] The present invention also provides a method for obtaining
an herbal composition capable of treating chronic stable angina
pectoris comprising steps of (a) applying Radix Notoginseng into
the multi-function extraction tank; add water until it is 15-20 cm
over the herb (about 5-7 times the quantity of the herb; heat up to
boiling with steam, while the inside air pressure should be
controlled in between 0.04-0.06 MPa; keeping the tank in boiling
condition, boiling twice, first for 2 hours and then for 1.5 hours,
filtering the extract at the bottom of the extraction tank through
a 100 mesh net into a stock tank, and discarding the remainder; (b)
Macroporous adsorption resin: (i) Pre-treatment of macroporous
adsorption resin: After being soaked in 95% ethanol for 24 hours,
non-polarity macroporous adsorption resin ZTC-1, With particle size
0.3-1.2 mm and average aperture 130-300 A, is filled into a column.
Wash the column with ethanol and equal volume of water until the
eluant is clear with equal volume of water; or after washing the
column with 0.1-1 mol/L NaOH or HCL, wash the column with water
until the eluant has no ethanol smell or is close to pH neutral,
(ii) Loading the extract of Radix Notoginseng from Step (a), 1 g/1
g resin with flow rate at 0.5-5 cm/cm.sup.2/min, washing the column
until the eluant is clear, Eluting with 70% ethanol. The flow rate
is 0.5-5 cm/cm.sup.2/min. Collect the eluant, (iii) Recovery resin.
Wash the column with 95% ethanol until the eluant is without color
and clear after adding equal volume of water. Then wash the column
with water until there is no ethanol smell; and (c) Applying the
75% ethanol eluant through 100 mesh net to a vacuum concentration
tank, adjusting the air input to 0.04-0.06 mPa and the vacuum to
-0.076.about.-0.088 mPa to keep the tank boiling but bumping.
Recover the ethanol until the density of the eluant reaches
1.33-1.35., thereby obtaining the extract of Notoginseng
saponin.
[0059] In addition, the present invention provide a method for
obtaining the dropping pellets of a herbal composition capable of
treating chronic stable angina pectoris comprising the steps of (a)
Mixing the Unctuous of the Radix Salviae Miltorrhizae and saponin
from Radix Notoginseng, boneol and poly 6000 in the melting tank by
stirring to homogenize the mixture, heating it to 80-85.degree. C.
by steaming, melting the mixture for 30-40 minutes until there are
no lump particles in the melted mixture; (b) Transferring the
melted mixture to the dropping pot of the dropping machine where
the temperature is about 89-93.degree. C.; The cooling solution is
liquid paraffin of which the temperature is lower than 8.degree.
C.; The inner diameter of the dropping head is 1.7 mm, and the
outer diameter of the dropping head is 2.4 mm. The distance between
the drug liquid and the dropping head is 5-6 cm; the distance
between the dropping head and the cooling solution is 26-31 cm. The
depth of the cooling solution is about 1 meter; The dropping speed
is 60-80 pellets/min; and (c) Take the dropping pellets from the
cooling oil and put them into a centrifuge for de-oilization; The
speed is 800-1100 r/min for 15 minutes, thereby producing dropping
pellets.
[0060] The present invention also provides the method above,
wherein the macroporous resins are packed in columns. The present
invention also provides the method above, wherein the
chromatographic material is selected from porous polymer, silicon
gel, aluminum oxide, polyamide, activated charcoal, cellulose or
sephadex in addition to macroporous resin (model D101). The present
invention further provides the method above, wherein the
chromatographic column eluate is concentrated at reduced pressure
under 60.degree. C. to a relative density of 1.33-1.35.
[0061] This invention provides an herbal composition, capable of
treating chronic stable angina pectoris, of which the outward
appearance is in a homogeneous round ball shape in the same
red-brown or brown-black color with aromatic smell, bitter taste.
This also invention provides the composition above, of which the
weight difference is about +15% within the range between
21.25-28.75 mg (average pellet weight is 0.02500 g, RED=0.21); the
density is 1.13-1.40 mg/mm.sup.3; and the diameter of the pellet is
0.33-0.34 cm, RED=3.42.
[0062] This invention provides the composition comprising the
product produced by the above methods. This invention also provides
a pharmaceutical composition comprising an effective amount of the
composition above and a pharmaceutically acceptable carrier. This
invention further provide the formulation above, wherein the
formulation is a pill, capsule, granule, tablet, suspension,
injection, syrup, or tincture.
[0063] This invention provides a method for treating stable angina
pectoris in a subject by administering to the subject an effective
amount of the above pharmaceutical compositions. This invention
also provides a method for improving ischemic electrocardiogram by
administering to the subject an effective amount of the above
pharmaceutical compositions. This invention further provides a
method for relieving angina pectoris by administering to the
subject an effective amount of the above pharmaceutical
compositions. In addition, this invention provides a method for
reducing the usage of nitroglycerin by administering to the subject
an effective amount of the above pharmaceutical compositions.
[0064] The present invention provides a method for relieving
palpitation by administering to the subject an effective amount of
the above pharmaceutical compositions. The present invention also
provides a method for decreasing cholesterol and triglyceride level
in blood for a subject with abnormal blood-lipid by administering
to the subject an effective amount of the above pharmaceutical
compositions. The present invention further provides a method for
decreasing platelet aggregation in blood by administering to the
subject an effective amount of the above pharmaceutical
compositions. In addition, the present invention also provides a
method for improving exercise tolerance and extending exercise
duration, interval between exercise initiation and angina
occurrence and interval between exercise initiation and 1 mm.
decrease of ST segment by administering to the subject an effective
amount of the above pharmaceutical compositions.
[0065] This invention provides a method for treating angina
pectoris of various kinds and degrees induced by coronary heart
diseases by administering to the subject an effective amount of the
above pharmaceutical compositions. This invention also provides a
method for antioxidizing and clearing free radicals by
administering to the subject an effective amount of the above
pharmaceutical compositions. This invention further provides a
method for treating brain injury caused by oxygen free
radical-induced lipid peroxidation by administering to the subject
an effective amount of the above pharmaceutical compositions. In
addition, This invention provides a method for treating hepatic
injury caused by oxygen free radical-induced lipid peroxidation by
caused by oxygen free radical-induced lipid peroxidation by
administering to the subject an effective amount of the above
pharmaceutical compositions.
[0066] This invention provides a method for treating chronic heart
disease caused by oxygen free radical-induced lipid peroxidation by
administering to the subject an effective amount of the above
pharmaceutical compositions. This invention also provides a method
for treating coronary heart disease caused by oxygen free
radical-induced lipid peroxidation by administering to the subject
an effective amount of the above pharmaceutical compositions. This
invention further provides a method for treating essential
hypertension by administering to the subject an effective amount of
the above pharmaceutical compositions.
[0067] The present invention provides a composition of the
medicament Dan Shen Pill (DSP) comprising (a) extracts of Radix
Salviae Miltorrhizae, water-soluble extracts of Panax ginseng, and
Borneol; (b) Radix Salviae Miltorrhizae, Notoginseng, borneol, and
carriers; and (c) Radix Salviae Miltorrhizae, Panax Notoginseng,
borneol, and pharmaceutical carriers.
[0068] The present invention provides the use of DSP for (a)
treating coronary heart disease; (b) treating coronary heart
disease in conjunction with other drugs; (c) primary prevention of
coronary heart disease; (d) primary prevention of coronary heart
disease in conjunction with other drugs; (e) secondary prevention
of coronary heart disease; (f) secondary prevention of coronary
heart disease in conjunction with other drugs; (g) reducing
glycerine intake by angina patients; and (h) reducing serum
cholesterol level.
[0069] The present invention further provides a method for
controlling the quality of medicaments by standarizing the
composition and the concentration of therapeutic substances in a
medicament by analyzing and identifying therapeutic components
using analytical techniques comprising the steps of (a)
fractionating a medicament using analytical techniques; and (b)
identifying and quantitating therapeutic substances contained in a
medicament by comparing with the analytical profile of the relevant
purified substances as standard.
[0070] The present invention further provides a dropping machine
for manufacturing a small-sized medicament, which can be readily
dissolved thus readily delivered to organs, comprising the parts of
(a) a dropping pot of which temperature is 60-100.degree. C.; (b)
liquid paraffin cooling solution of which temperature is lower than
8.degree. C.; (c) a dropping head with 1.8 mm inner diameter and
2.35 mm outer diameter; (d) a dropping head distanced from the
surface of cooling solution by approximately 15 cm; (e) a dropping
head distanced form the cooling solution by approximately 0.5-1.5
M; and (f) a dropping head with the speed of over 30 pellets per
minute.
[0071] This invention provides a method of treating and preventing
cardiovascular diseases with a composition, wherein said
composition comprises 1-10% Panax Notoginseng extracts. This
invention also provides a method of treating and preventing
cardiovascular diseases with a composition, wherein said
composition comprises 5-40% Radix Salviae Miltorrhizae extracts.
This invention further provides the method above, wherein said
composition comprises 1-5% Borneol additionally. In addition, this
invention provides the method above, wherein said composition
further comprises 1-5% Borneol. And this invention provides the
method above, wherein said composition comprises 1-5% Borneol
additionally.
[0072] This invention provides a method of treating and preventing
cardiovascular disease coronary heart disease comprising the step
of administering an effective amount above to the subject. This
invention also provides a method for treating and preventing
cardiovascular disease comprising the step of administering an
effective amount above in conjunction with other drugs to the
subject. This invention further provides a method of reducing
nitroglycerin intake, wherein said method comprising the step of
administering an effective amount above. In addition, this
invention provides a method for reducing serum cholesterol level,
wherein said method comprising the step of administering an
effective amount of claim above.
[0073] The present invention provides a method of determining
whether pharmaceutical compositions are capable of treating and
preventing cardiovascular disease, wherein said method comprising
the steps of (a) fractionating pharmaceutical compositions by high
performance liquid chromatography (HPLC); (b) comparing the
retention time of the fractions of pharmaceutical compositions with
the retention time of saponin R1, saponin Rg1 and saponin Re; and
(c) determining if pharmaceutical compositions contain fractions of
which retention time is equivalent to the retention time of saponin
Ri, saponin Rg, and saponin Re.
[0074] The present invention also provides a method of determining
if pharmaceutical compositions are capable of treating and
preventing cardiovascular disease, wherein said comprising the
steps of (a) fractionating a pharmaceutical composition by thin
layer chromatography (TLC); (b) comparing the position and color of
the fractions of pharmaceutical compositions with the position and
color of 3,4-dihydroxyphenyl lactic acid and protocatechuic
aldehyde; and (c) determining if pharmaceutical compositions
contain the fractions of which position and color are equivalent to
the position and the color of 3,4-dihydroxyphenyl lactic acid and
protocatechuic aldehyde.
[0075] Finally, the present invention provides a method of
determining if pharmaceutical compositions capable of treating and
preventing cardiovascular diseases, herein said method comprising
the steps of (a) treating heart muscles with or without
pharmaceutical compositions; (b) comparing the rate of calcium
influx in heart muscles treated without and with pharmaceutical
compositions; and (c) determining if pharmaceutical compositions
reduced the calcium influx to hear muscles.
[0076] This invention discloses a composition of the medicament Dan
Shen Pill (DSP) comprising:
[0077] (a) water-soluble extracts of Radix Salviae Miltorrhizae,
water-soluble extracts of Panax Notoginseng, and synthetic
Borneol;
[0078] (b) Radix Salviae Miltorrhizae, Notoginseng, borneol, and
carriers; and
[0079] (c) Radix Salviae Miltorrhizae, Panax Notoginseng, borneol,
and pharmaceutical carriers.
[0080] In an embodiment of the above medicament, Radix Salviae
Miltorrhizae and Panax Notoginseng are employed as they are used in
China for treating coronary heart disease since 200 AD. Panax
Notoginseng has been used to treat angina and Radix Salviae
Miltorrhizae has been used to promote blood circulation. Borneol is
employed to facilitate the fast delivery of therapeutic components
to target organs. Natunal Borneol has been used in China since 600
AD. As Borneol is almost extinct, DSP comprises synthetic
borneol.
[0081] This invention provides the use of DSP for:
[0082] (a) treating coronary heart disease;
[0083] (b) treating coronary heart disease in conjunction with
other drugs;
[0084] (c) primary prevention of coronary heart disease;
[0085] (d) primary prevention of coronary heart disease in
conjunction with other drugs;
[0086] (e) secondary prevention of coronary heart disease;
[0087] (f) secondary prevention of coronary heart disease in
conjunction with other drugs; and
[0088] (g) reducing nitrates intake by angina patients; and
[0089] (h) reducing serum cholesterol level.
[0090] In an embodiment of DSP, the indication is for coronary
artherosclerotic disease such as, but not limited, to alleviate
angina pectoris, to prevent angina pectoris caused by exertion and
stress, and to promote blood circulation by inhibiting platelet
aggregation thus to preventing coronary thrombus formation. DSP can
be applied to reduce nitroglycerine intake which is frequently used
to alleviate and to prevent angina. DSP can be also applied to
reduce plasma cholesterol level thus to prevent the formation of
new atherosclerosis lesions. Atherosclerosis is often initiated by
cholesterol streak deposited on vessel walls.
[0091] This inventions discloses a method for controlling the
quality of medicaments by standarizing the composition and the
concentration of therapeutic substances in a medicament by
analyzing and identifying therapeutic components using analytical
techniques comprising the steps of:
[0092] (a) fractionating a medicament using analytical techniques;
and
[0093] (b) identifying and quantitating therapeutic substances
contained in a medicament by comparing with the analytical profile
of the relevant purified substances as standard.
[0094] In an embodiment of the above invention, examples of
analytical techniques are thin-layer chromatography, high
performance liquid chromatography, and others. The purified
standard of therapeutic components are the major identified active
components in medicaments. For example, the purified standards of
active components for DSP are, but not limited to, saponins,
phenolic acid such as Danshensu, borneol, etc. Active components in
DSP are identified by comparing the position of DSP fractions such
as retention time in high performance liquid chromatography or the
position and the color of DSP fractions in thin-layer
chromatography, etc. with the characteristic of purified standards.
Active components of DSP is quantitated by comparing the size of
active fractions of DSP with the size of the known amount of
standards. For example, the amount of saponin contained in DSP is
determined by comparing with the standard curve of the known amount
of purified saponin.
[0095] In another embodiment, DSP comprises 5-40% water-soluble
phenolic acid of Radix Salviae Miltorrhizae, 1-10% water soluble
saponin of Panax Notoginseng, and 1-5% borneol.
[0096] In another embodiment, DSP comprises 10-30% water-soluble
phenolic acid of Radix Salviae Miltorrhizae, 2-6% water soluble
saponin of Panax Notoginseng, and 1-3% borneol.
[0097] This invention discloses a dropping machine for
manufacturing a small-sized medicament, which can be readily
dissolved thus readily delivered to organs, comprising the parts
of:
[0098] (a) a dropping pot of which temperature ranges 60-100; more
preferably 89-93.degree. C.;
[0099] (b) liquid paraffin cooling solution of which temperature is
lower than 8.degree. C.;
[0100] (c) a dropping head with 1.8 mm inner diameter and 2.35
outer diameter;
[0101] (d) a dropping head distanced from the surface of cooling
solution by approximately 15 m; and
[0102] In an embodiment of the use of the above machine is to
manufacture small-sized pills which can be dissolved immediately
upon administration.
[0103] In another embodiment, the size of small pills are:
[0104] (a) 0.33-0.34 cm in diameter;
[0105] (b) 21.25-28.75 mg in weight; and
[0106] (c) 1.13-1.40 mg/mm.sup.3 in density.
[0107] This invention provides a composition comprising extracts
from the following herbal materials in weight proportion: Radix
Salviae Miltorrhizae 48%.about.97%; Panax Notoginseng 2%
.about.50%; and Borneol 0.2%.about.3%.
[0108] In an embodiment, the weight proportions are: Radix Salviae
Miltorrhizae 63.0% .about.94%; Panax Notoginseng 4.0%.about.35.0%;
and Borneol 0.5% .about.2.0%.
[0109] In another embodiment, the weight proportions are: Radix
Salviae Miltorrhizae 75.2%18 90%; Panax Notoginseng 9%.about.23.5%;
and Borneol 0.5%.about.1.3%.
[0110] In a further embodiment, the weight proportions are: Radix
Salviae Miltorrhizae 82.87%; Panax Notoginseng 16.21%; and Borneol
0.92%.
[0111] The extraction of these herbal materials has been
exemplified below. Other extraction methods may be employed. The
biological activity of the resulting composition containing the
extracts can compare with the extracts described herein.
Accordingly, it is the intention of this disclosure to include
other enabling extraction technologies.
[0112] The present invention provides a pharmaceutical composition
comprising the above composition and a pharmaceutically acceptable
carrier.
[0113] For the purposes of this invention, "pharmaceutically
acceptable carriers" means any of the standard pharmaceutical
carriers. Examples of suitable carriers are well known in the art
and may include, but are not limited to, any of the standard
pharmaceutical carriers such as a phosphate buffered saline
solution and various wetting agents. Other carriers may include
additives used in tablets, granules and capsules, etc. Typically
such carriers contain excipients such as starch, milk, sugar,
certain types of clay, gelatin, stearic acid or salts thereof,
magnesium or calcium stearate, talc, vegetable fats or oils, gum,
glycols or other known excipients. Such carriers may also include
flavor and color additives or other ingredients. Compositions
comprising such carriers are formulated by well-known conventional
methods.
[0114] The present invention provides a pharmaceutical composition
for treating coronary heart disease and angina pectoris comprising
effective amount of extracts of Radix Salviae Miltorrhizae, Panax
Notoginseng and Borneol. The present invention also provides the
composition above wherein the Borneol is synthetic. The present
invention further provides the composition above comprising
effective amount of the composition from the above steps. In
addition, the present invention provides a method for treating a
subject with coronary heart disease comprising administering to the
subject the pharmaceutical composition above and the method above
wherein the subject is a human.
[0115] The invention provides a method for producing a composition
of Radix Salviae Miltorrhizae, Panax Notoginseng and Borneol
comprising steps of (a) obtaining appropriate amount of smashed
Radix Salviae Miltorrhizae and Panax Notoginseng; (b) extracting
the obtained Radix Salviae Miltorrhizae, Panax Notoginseng in hot
aqueous reflux; (c) combining the extracts to form a combined
extract; (d) concentrating the combined extract to perform alcohol
precipitation to obtain a supernatant; (e) eliminating the alcohol
of the supernatant to obtain a concentrated extract; (f) mixing the
concentrated extract from step e with appropriate amount of
borneol, thereby producing the composition of Radix Salviae
Miltorizae, Panax Notoginseng and Borneol.
[0116] As used herein, the alcohol includes but is not limited to
other alcohol appropriate for organic extraction. In a preferred
embodiment, the alcohol is an ethanol.
[0117] The present invention also provides the method above wherein
step b the temperature is between about 60 to about 100
.quadrature.. The present invention further provides the method
above wherein step c, the extracts are filtered before
combination.
[0118] In addition, the present invention provides the method above
wherein step the ratio of the volume of the concentrated extract to
the weight of inputting herbal materials being 1 liter:
0.7.about.1.3 kg. And the present invention provides the method
above wherein step d the final concentration of ethanol is about
50-85%, wherein step d the final ethanol concentration is about
69-71%.
[0119] This invention provides the method above wherein step d the
ethanol precipitation is performed for 4-24 hours, and wherein step
d the ethanol precipitation for 8-12 hours. This invention also
provides the method above, wherein the supernatant obtained in step
d is filtered prior to the elimination of the alcohol. This
invention further provides the method above wherein step e the
concentrated extract is to forma plaster of about 1.15-1.45 in
relative density. In addition, this invention provides the method
above wherein step e the concentrated extract is to form a plaster
of about 1.32-1.40 in relative density. And, this invention
provides the method above wherein the borneol is synthetic.
[0120] This invention provides the method above further comprising
packing the produced composition into the form of a powder, syrup,
tea, tincture, injection, topical solution, capsule, pill, granule,
tablet, nebula, suppository microcapsule or other pharmaceutically
acceptable forms.
[0121] This invention also provides the method above wherein the
formation of the pill comprising steps of (i) mixing the
concentrated extract plaster from step e, borneol and other
ingredients; (ii) heating to melt mixture and transfer it to a pill
maker; (iii) pouring the melted mixture into paraffin oil at a low
temperature; (iv) removing the paraffin oil; and (v) selecting the
pills.
[0122] The present invention provides a method above wherein the
other ingredient is a pharmaceutically acceptable carrier. The
present invention also provides a method above wherein the other
ingredient is Polyethylene glycol-6000 with a freezing point of
about 53.about.58.quadrature.. The present invention further
provides a method above wherein the other ingredient is
Polyethylene glycol-6000 and the amount added is 2-6 times in
weight of the concentrated extract and borneol. In addition, the
present invention provides a method above wherein the Polyethylene
glycol-6000 added is 3 times in weight of the concentrated extract
and borneol.
[0123] This invention provides a method above wherein the
temperature for melting the mixture is about 60-100 .quadrature..
This invention also provides a method above wherein the temperature
for melting the mixture is about 85-90 .quadrature.. This invention
further provides a method above wherein the temperature of paraffin
oil is about 0-10 .quadrature.. In addition, this invention
provides a method above wherein the temperature of paraffin oil is
about 5-10 .quadrature.. And, this invention provides a method
above wherein the temperature of paraffin oil is about 7-8
.quadrature..
[0124] This invention provides a method above wherein the weight of
the pills are measured in about 5-50 mg/pill and 1.95-4.29 mm in
diameter. This invention also provides a method above wherein the
weight of the pills are measured in 25.+-.15% mg/pill and
3.34.+-.15% mm in diameter.
[0125] The present invention provides the composition produced by
steps of method above. The present invention also provides a
pharmaceutical composition comprising the composition above and a
pharmaceutically acceptable carrier. The present invention further
provides the pharmaceutical composition above wherein the Borneol
is synthetic. In addition, the present invention provides the
pharmaceutical composition above for treating coronary heart
disease. And, the present invention provides the pharmaceutical
composition above for treating angina pectoris.
[0126] The present invention provides a method for increasing blood
volume in coronary artery, relaxing the smooth muscles of blood
vessels, improving the peripheral circulation, raising the oxygen
content in veins, or significantly improving the acute myocardial
ischemia or myocardial infarction in a subject comprising
administering to the subject an effective amount of the composition
above.
[0127] The present invention also provides a method for protecting
the cells from damage by hypoxia, anoxia, deoxygenation or
re-oxygenation by contacting said cells with effective amount of
the composition above.
[0128] The present invention further provides a method for
protecting the cells from damage by hypoxia, anoxia, deoxygenation
or re-oxygenation in a subject comprising administering to the
subject an effective amount of the composition above.
[0129] This invention provides a method for protecting cells
suffering from myocardial ischemia by contacting said cells with
effective amount of the composition above. This invention also
provides a method for protecting cells suffering from myocardial
ischemia in a subject comprising administering to the subject an
effective amount of the composition above. This invention further
provides a method for improving micro-circulation in a subject
comprising administering to the subject an effective amount of the
composition above. In addition, this invention provides a method
for preventing arrhythmia in a subject comprising administering to
the subject an effective amount of the composition above.
[0130] This invention provides a method for preventing platelets
aggregation, thrombosis and dissolve fibrin in a subject comprising
administering to the subject an effective amount of the composition
above. This invention also provides a method for lowering blood
viscosity, adjusting the blood cholesterol or preventing
atherosclerosis in a subject comprising administering to the
subject an effective amount of the composition above. This
invention further provides a method for raising the tolerance to
hypoxia, anoxia, preventing the oxidation of lipoprotein or
removing the harmful free radicals in a subject comprising
administering to the subject an effective amount of the composition
above. In addition, this invention provides a method for lowering
plasma ET content, significantly improve the liver, kidneys and
pancreas functions in a subject comprising administering to the
subject an effective amount of the composition above.
[0131] This invention provides a method for preventing the
occurrence or development of blood vessel or nerve diseases in a
subject comprising administering to the subject an effective amount
of the composition above. This invention also provides a method for
enhancing the immune system in a subject comprising administering
to the subject an effective amount of the composition above. This
invention further provides a method for regulating the vascular
nervous balance in a subject comprising administering to the
subject an effective amount of the composition above. In addition,
this invention provides a method for preventing and treatment
cardiovascular and cerebrovascular diseases, kidney disease, liver
disease, pneumonia, lung or heart disease, pancreatitis, diabetes,
vertebral disease, optic vessels disease, optic nerves disease,
eccentric headache, chronic stomachitis, dizziness, bone diseases,
altitude diseases, common elderly diseases in a subject comprising
administering to the subject an effective amount of the composition
above.
[0132] This invention provides a method for treating stable angina
pectoris, unstable angina pectoris, aged angina pectoris,
non-symptomatic myocardial ischemia, different types of coronary
heart diseases or angina pectoris diseases in a subject comprising
administering to the subject an effective amount of the composition
above. This invention also provides a method for treating
arrhythmia, enlargement of left ventricle, myocarditis, myocardial
infarction or cerebral infraction in a subject comprising
administering to the subject an effective amount of the composition
above. This invention further provides a method for rapidly
relieving coronary heart disease or angina pectoris in 3-10 minutes
when it is taken sublingually in a subject comprising administering
to the subject an effective amount of the composition above. In
addition, this invention provides a method for treating
hyperlipidaemia, high blood viscosity syndrome or high blood
pressure in a subject comprising administering to the subject an
effective amount of the composition above.
[0133] This invention provides a method for treating coronary heart
disease and high blood pressure, coronary heart disease and
hyperlipidaemia, coronary heart disease, enlargement of left
ventricles and coronary heart disease or arrhythmia in a subject
comprising administering to the subject an effective amount of the
composition above. This invention also provides a method for
treating diseases caused by micro-circulation disorder in a subject
comprising administering to the subject an effective amount of the
composition above. This invention further provides a method for
treating stroke, cerebral infarction, cerebral bleeding and other
cerebral diseases in a subject comprising administering to the
subject an effective amount of the composition above. In addition,
this invention provides a method for treating hepatitis B, chronic
liver fibrosis, liver fibrosis, active liver cirrosis, liver
cirrosis in compensation period and other related diseases in a
subject comprising administering to the subject an effective amount
of the composition above.
[0134] This invention provides a method for treating kidney
syndrome and its conjunctive diseases in a subject comprising
administering to the subject an effective amount of the composition
above. This invention also provides a method for treating diabetes
or its conjunctive diseases in a subject comprising administering
to the subject an effective amount of the composition above. This
invention also provides a method for treating cyanosis-typed optic
vessels diseases such as venal blockage in retina, central optic
artery blockage in retina, high blood pressure optic
atherosclerosis in retina, diabetic retinopathy, cento-neuropathy,
cento-osmotic neuropathy, ischemic neuropathy, optic neuritis or
optic nervous dystrophy in a subject comprising administering to
the subject an effective amount of the composition above. This
invention further provides a method for treating dizziness caused
by cerebral-arterial ischemia, Meniere's disease, high blood
pressure, coronary heart disease in a subject comprising
administering to the subject an effective amount of the composition
above. In addition, this invention provides a method for enhancing
the immune system in a subject comprising administering to the
subject an effective amount of the composition above.
[0135] This invention provides a method for regulating the vascular
nervous balance in a subject comprising administering to the
subject an effective amount of the composition above. This
invention also provides a method for treating detrimental death of
epicondylus medialis, femoral end necrosis, twisted joint, ligament
damage, fracture and proliferation of bone cells in a subject
comprising administering to the subject an effective amount of the
composition above. This invention further provides a method for
treating bronchitis in children in a subject comprising
administering to the subject an effective amount of the composition
above. In addition, this invention provides a method for treating
hypoxia or anoxia in a subject comprising administering to the
subject an effective amount of the composition above. And finally,
this invention provides a method for treating Alzhemier's Disease
in a subject comprising administering to the subject an effective
amount of the composition above.
[0136] Experimental Details
[0137] First Series of Experiments
[0138] Manufacturing of Dan Shen Pill (DSP)
[0139] DSP is a small pill, approximately 25 mg, of which
therapeutic components comprise water-soluble extracts of
Notoginseng, water soluble extracts of Salviae, and synthetic
borneol.
[0140] For manufacturing DSP, Notoginseng and Salviae are extracted
separately with hot water in circulating systems and filtered. The
filtrates are condensed under decompressed conditions, filtered and
precipitated. The concentrates are refined using resin columns and
concentrated under decompressed conditions. The refined
water-soluble extracts thus obtained were mixed with synthetic
Borneol and pharmaceutical carriers. The mixture is made to a small
pill using a special dropping machine. The quality of DSP is
controlled by standarizing the quantity as well as the proportion
of its major therapeutic components Saponon, phenolic acid such as
Danshensu and Borneol. Thin-layer chromatography, high performance
liquid chromatography, fingerprinting and other analytical
techniques are used to identify and quantitate therapeutic
components in DSP.
[0141] Manufacturing of DSP
[0142] 1. Extraction of water-soluble components of Panax
Notoginseng
[0143] (a) Dilution of herbs with 5-7 times of water.
[0144] (b) Extraction of water-soluble components of Panax
Notoginseng by boiling in a tank with the air pressure between
0.04-0.06 mPa for 2 hours.
[0145] (c) Repeat extraction under the same condition for 1.5
hours.
[0146] (d) Filtration of the extraction with 100-mesh net.
[0147] (e) Refine the filtrate using macroporous adsorption resin
eluting with ethanol.
[0148] (g) Concentration of the eluted extracts under decompressed
condition with the air input to 0.04-0.06 mPa and the vacuum to
-0.076.about.-0.088 mPa until the density is 1.33-1.35.
[0149] 2. Extraction of water-soluble components of Radix Salviae
Miltorrhizae
[0150] (a) Dilution of herbs with 5-7 times of water.
[0151] (b) Extraction of water-soluble components of Radix Salviae
Miltorrhizae by boiling in a tank with the air pressure between
0.04-0.06 mPa for 2 hours.
[0152] (c) Repeat extraction under the same condition for 1.5
hours.
[0153] (d) Filtration of the extraction with 100-mesh net.
[0154] (e) Concentration of the filtrates under decompressed
conditions with the vacuum pressure is-0.076.about.--0.088 mPa
until one Kg initial herb becomes one liter.
[0155] (f) Precipitation of the concentrates with ethanol.
[0156] (g) Filtration of the ethanol precipitates solution through
100-mesh net.
[0157] (h) Concentration of the filtrates under decompressed
conditions with input air pressure is 0.04-0.06 mPa and the vacuum
pressure is 0.076.about.-0.088 mPa.
[0158] (i) Refine the concentrates by polyamide chromatography
eluting with ethanol.
[0159] (j) Concentrate the refined extracts to the density of
1.33-1.35.
[0160] 3. DSP production
[0161] (a) Mix the extracts of Panax Notoginseng, the extracts of
Radix Salviae Miltorrhizae, synthetic boneol and polyethylene
glycol 6000 at the ratio of 4.0:20.6:1.9:79.5.
[0162] (b) Melting the mixture.
[0163] (c) Manufacturing the melted mixture to DSP using the
dropping machine with the following characteristics: the
temperature of dropping pot is constantly 89-93.degree. C., the
cooling solution is liquid paraffin of which the temperature is
lower than 8.degree. C., the inner diameter of the dropping head is
1.8 mm, the outer diameter of the dropping head is 2.4 mm, the
distance between the dropping head and the surface of cooling
solution is 15 cm.
[0164] (d) Centrifugation of the pills at 800-1100 rpm for 15
minutes to remove oils.
[0165] Quality Control of DSP
[0166] DSP contains the identified therapeutic components
protocatechuic aldehyde and saponin as well as various other
components. The contents of these compounds in herbs vary from lot
to lot of herbs. To standarize the contents of therapeutic
components in DSP and thus to control the quality of DSP, a method
to identify and to quantitate therapeutic agents in medicaments has
been developed. An example of the procedures comprises:
[0167] (a) Dissolve 30 DSPs in 3 ml methanol and ultrasonicate for
10 minutes.
[0168] (b) Centrifugation for 5 minutes.
[0169] (c) Fractionate the supernatant using standard analytical
techniques using thin layer chromatography, high performance liquid
chromatography, etc.
[0170] (d) Identification of the therapeutic components of DSP such
as Sodium Danshensu, protocatechuic aldehyde, saponin, etc. by
comparing DSP fractions with the relevant purified standards in
regard to the position, size and color.
[0171] (e) Identifying and quantitating therapeutic components in
DSP by comparing the position, size, and color of DSP fractions
with the position, size and color of the relevant purified
standards.
[0172] (f) Identifying therapeutic components in DSP by comparing
the relative retention time and relative area of peaks in
fingerprints with the relative retention time and relative area of
peaks in standard fingerprint.
[0173] TLC Identification of DSP
[0174] A method for identifying Sodium Danshensu and protocatechuic
aldehyde of a herbal composition capable of treating chronic stable
angina pectoris by thin layer chromatography comprising the steps
of:
[0175] a) preparing the assay comprising the steps of:
[0176] i. putting 30 pellets of the said composition in 3 ml
methanol and dissolve by ultrasonation for 10 minutes to form a
solution;
[0177] ii. centrifuging the solution for 5 minutes and collect the
supernatant;
[0178] iii. contacting 10 ul the solution onto a silicon G gel
plate containing 0.5% CMC-Na;
[0179] iv. developing the plate with a developing solution
comsisting of Chloroform, acetone and methane acid in the ratio of
10:4:1.6;
[0180] v. drying and fumigating the plate with ammonia and laying
the plate up for 15 minutes;
[0181] vi. checking the plate under ultraviolet light, the spot
representing the said composition should be at the corresponding
position of the standards and show the same color.
[0182] b). using Sodium Danshensu and protocatechuic aldehyde as
the standards.
[0183] A method for identifying gypenoside of a herbal composition
capable of treating chronic stable angina pectoris by thin layer
chromatography comprising the steps of:
[0184] a) preparing the assay comprising the steps of:
[0185] i. Put 30 pellets of the said composition in 5 ml ammonia
solvent and dissolve by ultrasonation to form a solution;
[0186] ii Put the said solution into the macroporous adsorption
resin column; the speed is 0.5/minute;
[0187] iii. After washing the macroporous adsorption resin column
with 20 ml distilled water, the macroporous adsorption resin column
is eluted with 2 ml methanol solution;
[0188] iv. collecting the-eluant;
[0189] v. contacting 10 ul said eluant onto a silicon G gel plate
containing 0.5% CMC-Na;
[0190] vi. developing the plate with 10 ml developing solution
which is a lower layer clarificant of the solution of Chloroform,
acetone and water in the ratio of 6:3:1 after 2 hours at
10.quadrature.C;
[0191] vii. After being dried and sprayed with 10% ethanol sulfate,
the plate is baked at 105[]C for several minutes;
[0192] viii. Check the plate under normal light, the spot
representing the said composition should be at the corresponding
position of the standards and show the same color.
[0193] b). using total gypenoside, Saponin R1 and ginsenoside Rg1
as the standards.
[0194] Fingerprints of Cardiotonic Pill
[0195] 1. Preparation of Fingerprints
[0196] (1) Chromatographic System and System Suitability
[0197] Alkyl silan-linking silico-18 was used as the stationary
phase, and the mixture of A and B as mobile phase. A was methanol
and B was the mixture of water- "N,N-dimethyl-formamide"-glacial
acetic acid (100:45:4). The concentration of A changes from 5% to
30% when time of gradient elution elapses from 0 to 25 minutes. The
detective wavelength was set at 281 nm. The number of theoretical
plates of the column was not less than 2000 when calculated with
the peak of Danshensu.
[0198] (2) Apparatus and Reagents
[0199] Chromatograph: HP 1100 Liquid Chromatograph
[0200] Detector: HP VWD-stile ultraviolet detector
[0201] Column: Alltech Company 5u, 250.times.4.6 mm, ODS column
[0202] Pre-column: Alltech Company, Alltima C.sub.18 5 u
pre-column
[0203] Temperature of the column: 30.degree. C.
[0204] (3) Preparation of the Control Sample
[0205] Salvianic acid B, Danshensu and protocatechuic aldehyde were
dissolved respectively in methanol to produce three control
solutions each ml containing 50 .mu.g, 40 .mu.g and 10 .mu.g
correspondingly.
[0206] (4) Preparation of the Test Sample
[0207] Put 10 pills of Cardiotonic Pill into a 25 ml measuring
flask, add 20 ml of methanol, ultrasonicate for 20 minutes, allow
to cool, dilute the solution to the scale-line with methanol,
centrifugate and take the supernate as the test solution.
[0208] (5) Procedure
[0209] Accurately inject 10 .mu.l each of the control solutions and
the test solution, respectively, into the column, record the
chromatograph chart and calculate the content.
[0210] 2. Fingerprints of Different Batches of Cardiotonic Pill
[0211] Twenty batches of Cardiotonic Pill samples were tested with
the above-described method, and statistical data is shown as Table
1, Table 2 and Table 3. These data revealed that Cardiotonic Pill
had specific fingerprint of its own and the fingerprints contained
eight common peaks, that is, these peaks should exist
simultaneously in each batch of DSP. Taking protocatechuic aldehyde
peak as reference peak, whose relative retention time was 1, the
average value of relative retention time of the eight peaks was
0.672, 1.000, 1.417, 1.512, 2.016, 2.235, 2.407, 2.757. The values
of relative retention time and relative area of the eight peaks
were very stable, and among the eight common peaks, peak No.1 was
Danshensu, peak No.2 protocatechuic aldehyde and peak No.7
Salvianic acid B, and the ratio of relative area value was
0.476-0.668:1:0.391-0.641, respectively.
[0212] Fingerprints of three batches of Cardiotonic Pill are also
provided as FIGS. 1 through 3.
2TABLE 1 The peak retention time & relative retention time of
20 batches of DSP Common Peaks Peak No. 1 Peak No. 2 Peak No. 3
Peak No. 4 Relative Relative Relative Relative Retention retention
Retention retention Retention retention Retention retention Batch
No. time time time time time time time time 19990806 8.347 0.676
12.341 1.000 17.662 1.431 18.802 1.524 19990815 8.313 0.676 12.305
1.000 17.631 1.433 18.769 1.525 19990823 8.285 0.672 12.338 1.000
17.498 1.418 18.673 1.513 19990921 8.302 0.672 12.350 1.000 17.553
1.421 18.739 1.517 19990928 8.299 0.672 12.352 1.000 17.549 1.421
18.727 1.516 19991014 8.290 0.672 12.344 1.000 17.496 1.417 18.677
1.513 19991026 8.295 0.672 12.337 1.000 17.513 1.420 18.673 1.514
19991109 8.286 0.672 12.329 1.000 17.477 1.418 18.642 1.512
19991127 8.291 0.672 12.341 1.000 17.502 1.418 18.660 1.512
19991205 8.291 0.672 12.340 1.000 17.500 1.418 18.659 1.512
20000106 8.287 0.672 12.338 1.000 17.503 1.419 18.664 1.513
20000216 8.294 0.671 12.352 1.000 17.536 1.420 18.687 1.513
20000323 8.256 0.670 12.329 1.000 17.402 1.411 18.606 1.509
20000406 8.272 0.670 12.349 1.000 17.428 1.411 18.628 1.508
20000422 8.274 0.670 12.348 1.000 17.425 1.411 18.609 1.507
20000513 8.276 0.670 12.350 1.000 17.439 1.412 18.611 1.507
20000606 8.273 0.670 12.347 1.000 17.421 1.411 18.597 1.506
20000726 8.283 0.670 12.356 1.000 17.413 1.409 18.598 1.505
20000728 8.287 0.670 12.368 1.000 17.487 1.414 18.653 1.508
20000804 8.274 0.670 12.351 1.000 17.434 1.412 18.597 1.506 Average
value 8.289 0.672 12.343 1.000 17.493 1.417 18.664 1.512 RSD %
0.225 0.266 0.104 0.000 0.398 0.447 0.313 0.362 Common Peaks Peak
No. 5 Peak No. 6 Peak No. 7 Peak No. 8 Relative Relative Relative
Relative Retention retention Retention retention Retention
retention Retention retention Batch No. time time time time time
time time time 19990806 25.090 2.033 27.805 2.253 30.047 2.435
34.146 2.767 19990815 25.072 2.038 27.793 2.259 30.046 2.442 34.092
2.771 19990823 25.034 2.029 27.742 2.249 29.897 2.423 34.186 2.771
19990921 25.005 2.025 27.715 2.244 29.875 2.419 34.155 2.766
19990928 24.968 2.021 27.661 2.239 29.804 2.413 34.070 2.758
19991014 24.903 2.017 27.604 2.236 29.743 2.410 34.019 2.756
19991026 24.889 2.017 27.600 2.237 29.747 2.411 34.017 2.757
19991109 24.852 2.016 27.571 2.236 29.722 2.411 34.014 2.759
19991127 24.882 2.016 27.594 2.236 29.737 2.410 34.026 2.757
19991205 24.862 2.015 27.569 2.234 29.708 2.407 34.007 2.756
20000106 24.867 2.015 27.576 2.235 29.721 2.409 34.026 2.758
20000216 24.887 2.015 27.590 2.234 29.730 2.407 34.066 2.758
20000323 24.869 2.017 27.561 2.235 29.644 2.404 34.067 2.763
20000406 24.843 2.012 27.534 2.230 29.613 2.398 34.012 2.754
20000422 24.799 2.008 27.493 2.227 29.572 2.395 33.975 2.751
20000513 24.791 2.007 27.479 2.225 29.553 2.393 33.944 2.749
20000606 24.755 2.005 27.451 2.223 29.524 2.391 33.918 2.747
20000726 24.744 2.003 27.440 2.221 29.513 2.389 33.925 2.746
20000728 24.807 2.006 27.500 2.223 29.573 2.391 34.001 2.749
20000804 24.746 2.004 27.441 2.222 29.515 2.390 33.941 2.748
Average value 24.883 2.016 27.586 2.235 29.714 2.407 34.030 2.757
RSD % 0.416 0.476 0.399 0.463 0.540 0.606 0.219 0.273
[0213]
3TABLE 2 The peak area value & area ratio of 20 batches of DSP
Common Peaks Peak No. 1 Peak No. 2 Peak No. 3 Peak No. 4 Area Area
Area Area Batch No. Area ratio Area ratio Area ratio Area ratio
19990806 1044.800 0.668 1563.800 1.000 269.790 0.173 240.540 0.154
19990815 834.300 0.576 1448.900 1.000 359.860 0.248 347.080 0.240
19990823 1036.100 0.576 1800.300 1.000 409.060 0.227 334.160 0.186
19990921 980.840 0.568 1726.000 1.000 379.050 0.220 317.920 0.184
19990928 1068.000 0.549 1943.800 1.000 397.230 0.204 329.450 0.169
19991014 984.660 0.589 1670.700 1.000 353.250 0.211 297.610 0.178
19991026 978.100 0.556 1758.900 1.000 348.520 0.198 282.550 0.161
19991109 974.320 0.603 1617.100 1.000 334.350 0.207 275.060 0.170
19991127 1053.800 0.565 1865.300 1.000 413.960 0.222 327.640 0.176
19991205 1089.600 0.564 1931.200 1.000 391.970 0.203 334.240 0.173
20000106 1130.800 0.571 1979.800 1.000 408.490 0.206 347.890 0.176
20000216 1114.900 0.548 2034.600 1.000 419.800 0.206 426.030 0.209
20000323 1080.000 0.599 1801.900 1.000 323.240 0.179 294.760 0.164
20000406 1132.600 0.583 1943.200 1.000 431.080 0.222 374.840 0.193
20000422 1124.400 0.508 2212.300 1.000 378.160 0.171 356.690 0.161
20000513 1088.200 0.564 1928.200 1.000 390.250 0.202 331.510 0.172
20000606 1033.200 0.575 1796.300 1.000 408.200 0.227 333.210 0.185
20000726 985.250 0.569 1730.200 1.000 382.510 0.221 322.210 0.186
20000728 1120.320 0.521 2148.500 1.000 410.920 0.191 385.540 0.179
20000804 831.320 0.577 1440.300 1.000 321.250 0.223 301.280 0.209
Average value 1034.276 0.572 1817.065 1.000 376.547 0.208 328.011
0.181 RSD % 8.486 5.612 11.452 0.000 10.914 9.354 12.553 11.003
Common Peaks Peak No. 5 Peak No. 6 Peak No. 7 Peak No. 8 Area Area
Area Area Batch No. Area ratio Area ratio Area ratio Area ratio
19990806 266.040 0.170 583.830 0.373 1001.800 0.641 1568.000 1.003
19990815 340.390 0.235 348.490 0.241 600.210 0.414 994.740 0.687
19990823 486.430 0.270 495.600 0.275 823.430 0.457 1632.800 0.907
19990921 498.570 0.289 479.530 0.278 875.440 0.507 1518.700 0.880
19990928 514.290 0.265 595.650 0.306 1092.700 0.562 1828.100 0.940
19991014 504.860 0.302 504.900 0.302 879.420 0.526 1378.000 0.825
19991026 451.380 0.257 416.600 0.237 800.660 0.455 1303.700 0.741
19991109 477.390 0.295 491.810 0.304 836.830 0.517 1302.800 0.806
19991127 499.750 0.268 521.160 0.279 1047.200 0.561 1643.800 0.881
19991205 468.210 0.242 521.600 0.270 890.080 0.461 1659.100 0.859
20000106 512.040 0.259 519.150 0.262 891.890 0.450 1747.000 0.882
20000216 570.720 0.281 521.100 0.256 1232.200 0.606 1767.500 0.869
20000323 562.520 0.312 602.060 0.334 1041.600 0.578 1544.700 0.857
20000406 609.180 0.313 655.030 0.337 1166.600 0.600 1642.400 0.845
20000422 574.650 0.260 692.970 0.313 1189.700 0.538 1758.300 0.795
20000513 466.050 0.242 518.200 0.269 886.300 0.460 1750.200 0.908
20000606 485.200 0.270 492.920 0.274 821.520 0.457 1613.200 0.898
20000726 502.350 0.290 483.060 0.279 880.210 0.509 1523.200 0.880
20000728 621.250 0.289 672.250 0.313 1178.200 0.548 1692.300 0.788
20000804 321.240 0.223 392.720 0.273 683.270 0.474 1081.360 0.751
Average 486.626 0.267 525.432 0.289 940.963 0.516 1547.495 0.850
value RSD % 18.592 12.698 16.851 11.766 18.292 12.061 14.739
8.647
[0214]
4TABLE 3 The statistical data of eight peaks derived from
fingerprints of 20 batches of DSP Relative Retention Retention
Appearance Area Peak No. Time Time Probability Area Ratio Area
Ratio Range 1 8.289 0.672 100% 1034.276 0.572 0.572 .+-. 0.096 2
12.343 1.000 100% 1817.065 1.000 1.000 .+-. 0.000 3 17.493 1.417
100% 376.547 0.208 0.208 .+-. 0.040 4 18.664 1.512 100% 328.011
0.181 0.181 .+-. 0.059 5 24.883 2.016 100% 486.626 0.267 0.267 .+-.
0.097 6 27.586 2.235 100% 525.432 0.289 0.289 .+-. 0.052 7 29.714
2.407 100% 940.963 0.516 0.516 .+-. 0.125 8 34.030 2.757 100%
1547.495 0.850 0.850 .+-. 0.163
[0215] Quantitative Analysis of Danshensu in DSP
[0216] Chromatography and systemic adaptive conditions, apparatus
and reagents:
[0217] 1. Preparation of Fingerprints
[0218] (1) The Parameters of Chromatogram & System
Adjustment.
[0219] Alkyl silan-linking silico-18 was used as filling material,
and water-acetonitrile-glacial acetic acid (87:12:1) as mobile
phase. Detective wave length was set at 281 nm. The number of
theoretical plate should not be less than 2500 when calculated with
the peak of Danshensu, and the degree of separation should meet the
requirements.
[0220] (2) Apparatus & Reagents
[0221] Chromatograph: HP 1100 Liquid Chromatograph
[0222] Detector: HP VWD-stile ultraviolet detector
[0223] Column: Alltech Company 5u, 250.times.4.6 mm, ODS column
[0224] Pre-column: Alltech Company, Alltima C18 5 u pre-column
[0225] Temperature of the column: 30.degree. C.
[0226] Acetonitrile: chromatographically pure, Tianjin Siyou
Biomedical & Technical Co. Ltd.
[0227] Glacial acetic acid: analytically pure, Tianjin Tianhe
Reagent Company.
[0228] (3) Preparation of the Control Sample.
[0229] Use 25.0 mg of sodium salvianic acid and 5.0 mg of
protocatechuic aldehyde as the control samples: Weigh both of the
samples accurately and put them into the 50 ml measuring flasks.
Add mobile phase to dissolve them and dilute the solutions up to
the scale-line of the flasks, shake them thoroughly and save them
as the stock solutions. Weigh a little amount of paraaminobenzoic
acid accurately, dissolve it as a solution of 0.2 mg/ml with the
mobile phase and take it as the internal standard stock solution.
Pipit proper amounts of sodium salvianic acid A, protocatechuic
aldehyde and internal standard solutions whit their volumes
accurately read, dilute them with the mobile phase to prepare a
solution that contained 50 ug of sodium salvianic acid A, 10 ug of
protocatechuic aldehyde and 80 ug of paraaminobenzoic acid. The
prepared solution was taken as the control solution.
[0230] (4) Preparation of the Test Sample.
[0231] Take 10 pills of Cardiotonic Pill and 1 ml of internal
standard stock solution, put them into a 25 ml measuring flask,
dissolve them with mobile phase, and dilute the solution to the
scale-line. Take 10 ml of the control and the test sample
solutions, respectively, make the injection and record the
chromatograph chart.
[0232] Preparation of the control solution: Take and weigh
accurately 25.0 mg of sodium tanshinol, and put it into a measuring
flask. Add the mobile phase, and dissolve and dilute it to the
scale. Shake the solution up, and keep it as the control stock
solution. Weigh para-aminobenzoic acid accurately and dilute it
into a 0.2 mg/ml solution with the mobile phase. Keep the solution
as the internal standard stock solution. Take appropriate doses of
the control stock solution and the internal standard stock
solution, and make them into the control solution comprising 50
.mu.g of sodium tanshinol and 80 .mu.g of para-aminobenzoic acid
per milliliter.
[0233] Preparation of the test solution: Take 10 pills of this
article and 1 ml of the internal stock solution. Put them in a 25
ml measuring flask, dissolve them to the scale and make them into
the test solution.
[0234] Take 101 of the control solution and 101 of the test
solution respectively, take down the fingerprints and calculate the
results.
[0235] The herbal composition comprising DSP should contains
0.14-0.18 mg Danshensu per pill.
[0236] Quantitative Analysis of Ginsenoside Rg1 and Sanchinoside R1
in DSP
[0237] (1) Chromatographic System and System Suitability
[0238] Alkyl silan-linking silico-18 was used as the stationary
phase, and the mixture of water and acetonitrile as mobile phase.
The concentration of acetonitrile was 25% from 0 to 15 minutes, and
35% after 15th minute. Nebulizer gas flowrate was 2.5 liter per
minute and drift tube temperature was set at 93.8.degree. C. The
number of theoretical plates of the column was not less than 5000
when calculated with the peak of Ginsenoside Rg1.
[0239] (2) Apparatus and Reagents
[0240] Chromatograph: Agilent 1100 Liquid Chromatograph
[0241] Detector: Alltech ELSD 2000 detector (evaporative light
scattering detector)
[0242] Column: Alltech Company 5u, 250.times.4.6 mm, ODS-C.sub.18
column
[0243] Pre-column: Alltech Company, Alltima C.sub.18 5 u
pre-column
[0244] Temperature of the column: 30.degree. C.
[0245] (3) Preparation of the Control Sample
[0246] Ginsenoside Rg1 and Sanchinoside R1 were dissolved
respectively in methanol to produce two control solutions each ml
containing 0.98 mg and 0.25 mg correspondingly.
[0247] (4) Preparation of the Test Sample
[0248] Put 50 pills of Cardiotonic Pill into a 5 ml measuring
flask, add 4% ammonia to the scale-line, ultrasonicate for 20
minutes, and apply the solution to a previously prepared small
C.sub.18 column (STRATA C18-E column of Phenomenex Company, 500 mg
and 3 cc tube), elute 10 ml of water, discard the eluate, then
elute 2 ml of methanol, collect the eluate in a measuring flask and
dilute it to the scale-line with methanol, take the solution as the
test solution.
[0249] (5) Procedure
[0250] Accurately inject 10 .mu.l each of the control solutions and
the test solution, respectively, into the column, record the
chromatograph chart and calculate the content.
[0251] (6) Result
[0252] Twenty batches of Cardiotonic Pill samples were tested with
the above-described method, and statistical data is shown as Table
4. Drawn on above table, the herbal composition comprising DSP
contains 0.401%.about.712%, average 0.550% Sanchinoside R1 and
2.069%-4.44%, average 2.847% Ginsenoside Rg1.
5TABLE 4 Quantities of Ginsenoside Rg1 and Sanchinoside R1 in DSP
Sanchinoside R1 Ginsenoside Rg1 Batch No. (.mu.g/pill) (.mu.g/pill
) 20000106 17.22 80.93 20000216 16.92 80.78 20000323 15.16 70.76
20000406 13.65 62.51 20000422 14.24 68.72 20000513 15.27 71.16
20000606 14.86 68.21 20000726 14.59 72.35 20000728 14.25 57.37
20000804 15.30 70.55 Average 15.15 70.33 value RSD % 7.53 9.67 not
less 12.12 56.26 than
[0253] The characteristics of DSP thus manufactured are as
follows:
[0254] (a) DSP contain b-3,4-dihydroxyphenyl lactic acid, sodium
danshensu, saponin, and borneol,
[0255] (b) negative for bacteria: contains less than 1,000
bacteria,
[0256] (c) negative for fungi: contains less than 100 fungi,
[0257] (d) negative for heavy metal: contains less than the safety
amount defined by the Chinese government.
[0258] (e) The shelf-life of DSP is four years at room
temperature.
[0259] Clinical Studies of DSP
[0260] Angina pectoris is evaluated by the history of angina, serum
lipid level, electrocardiography (ECG), exercise ECG,
scintiographic assessment of ischemia, coronary angiography, etc.
Assessing therapeutic efficacy using these end points, DSP has been
shown to be effective for treating angina pectoris.
[0261] DSP is Effective for Angina Pectoris.
[0262] 157 patients with coronary heart disease were treated with
10 DSPs per t.i.d., oral administration for 4 weeks. Assessing the
frequency, intensity and duration of angina, oppressed feeling in
chest and palpitation, the symptoms were disappeared or remitted in
95.3% patients.
[0263] DSP is more Efficient than Dan Shen Tablets in Alleviating
Angina.
[0264] Dan Shen tablet is another Chinese medicament for treating
angina pectoris currently used in China. The efficacy of DSP and
Dan Shen tablet was compared. Coronary heart disease patients were
randomly divided into two groups. 107 patients were treated with
DSP and 50 patients were treated with Dan Shen Tablet. Comparing
the frequency of angina attacks and the consumption of nitrates,
DSP was more effective than Dan Shen Tablets for treating angina
pectoris. See Table 5 below.
6TABLE 5 Comparison of DSP and Dan Shen tablet Number of patients
Total Responsive DSP 107 102 (95.3%) Dan Shen tablet 50 38
(76%)
[0265] Having proven that DSP is more effective than Dan Shen
tablets, the efficacy of DSP was compared with various drugs which
are currently used for treating chronic stable angina pectoris in
the US.
[0266] Comparison of DSP and Nitroglycerine
[0267] Nitroglycerine is the frequently used to relieve angina. The
efficacy of DSP and nitroglycerine relieving angina was compared.
At the onset of angina, patients were treated with either DSP or
nitroglycerine, and the time required to alleviate angina was
compared. Both DSP and nitroglycerine alleviate angina in all
patients within 15 minutes. The efficacy of DSP was slightly lower
than nitroglycerine. See Table 6 below.
7TABLE 6 Comparison of DSP and nitroglycerine # patients responded
within 1-5 minutes 6-10 minutes 11-15 minutes DSP 11 14 5
Nitroglycerine 17 12 1 Total: 30 patients per group
[0268] DSP does not Change Heart Rate
[0269] The data demonstrate that DSP effectively alleviate angina.
It was examined whether DSP relieves anginal by increasing heart
rate. The heart rate after DSP treatment was equivalent to the
pretreatment rate, which indicates that DSP relieves angina without
affecting heart rate (Table 7).
8TABLE 7 DSP does not affect heart rate Heart rate Pretreatment
Post -treatment DSP 84.3 .+-. 23.1 82.8 .+-. 22.8 Comparison of the
efficacy of DSP with the nitrate isosorbide
[0270] Dinitrate
[0271] Having proven that DSP alleviate angina as efficiently as
nitroglycerin, it was examined whether DSP can prevent angina. The
efficacy of DSP and the nitrate isosorbide dinitrate was compared.
Isosorbide dinitrate is a long-acting nitrate frequently used for
preventing chronic stable angina pectoris in the US. Patients were
treated with either DSP three times per day orally 10 pills per
treatment or Isosorbide dinitrate three times per day orally 10 mg
per treatment. Cardiac function and Electrocardiogram was
examined.
[0272] Cardiac Function.
[0273] The efficacy of DSP and nitrates on cardiac function was
evaluated by measuring cardiac output per stroke (CO), stroke
volume per minute (SV), eject blood fraction (EF), fraction of
shortened rate of left ventricular short axis (FS). DSP improves
cardiac function more efficiently than nitrates. See Table 8
below.
9TABLE 8 The effect of DSP and nitrates on cardiac function DSP
Isosorbide initrate Pre- Post- Pre- Post SV 75.38 .+-. 8.32 83.45
.+-. 9.11 74.96 .+-. 8.44 79.47 .+-. 8.72 CO 5.61 .+-. 1.34 6.94
.+-. 1.36 6.54 .+-. 1.36 6.12 .+-. 1.41 EF 0.57 .+-. 0.02 0.79 .+-.
0.02 0.59 .+-. 0.03 0.70 .+-. 0.03 FS 17.14 .+-. 3.4 16.69 .+-. 3.6
17.32 .+-. 3.1 18.46 .+-. 4.2 Pre-: preteatment Post-:
post-treatment
[0274] DSP Improves ECG
[0275] The ST-T effective rate was evaluated by recording the
frequency of change in the ST-T segment. Both DSP and isosorbide
dinitrates decreased the frequency of change in ST-T significantly.
DSP, however, was more efficient. See Table 9 below.
10TABLE 9 Comparison of the effect of DSP and nitrate on ECG The
frequency of ST-T change Pretreatment Post -treatment DSP 131 35
isosorbide dinitrate 129 42
[0276] Comparison of DSP and Aspirin in Reducing Blood Stasis
[0277] Hemorrhage at the atherosclerotic lesions induces platelet
activation, coronary thrombosis and blood stasis resulting in
impaired blood flow. Thus to improve blood flow, chronic
administration of the platelet-activation inhibitor aspirin is
recommended for patients with angina. The efficacy of DSP and
aspirin improving blood flow was compared by evaluating [Hb, Lb, P
and air flow]. DSP improves blood flow as efficiently as aspirin.
DSP improves blood flow as efficiently as aspirin. See Table 10
below.
11TABLE 10 DSP and aspirin improve blood flow DSP aspirin Pre-
Post- Pre- Post- Hb 6.23 .+-. 1.67 4.35 .+-. 1.02 6.12 .+-. 1.56
4.28 .+-. 1.07 LB 10.92 .+-. 2.21 8.30 .+-. 1.14 10.38 .+-. 1.96
8.21 .+-. 0.3 P 1.95 .+-. 0.08 1.77 .+-. 0.08 1.89 .+-. 0.12 1.67
.+-. 0.7 Air 1.79 .+-. 0.13 1.39 .+-. 0.11 1.82 .+-. 0.17 1.40 .+-.
0.10 flow Total number of patients: 25 for DSP and 28 for
aspirin
[0278] DSP Reduces Blood Stasis by Inhibiting Platelet
Activation
[0279] Thromboxane B2 activates platelet. Activated platelets
release various substances including .beta. platelet microglobulin,
which causes blood stasis, thus impairing blood flow. The efficacy
of DSP inhibiting platelet activation was examined. DSP lowers
thromboxane B2 concentration and inhibits platelet aggregation
efficiently. Isosorbide dinitrate, which is known to be unable to
inhibit platelet activation thus used as control, did not reduce
thromboxane B2 or inhibit platelet activation. See Table 11
below.
12TABLE 11 DSP inhibits platelet activation Pretreatment
Post-treatment .beta. PM DSP 62.44 .+-. 14.37 45.65 .+-. 12.25
nitrates 59.89 .+-. 15.42 54.36 .+-. 13.18 Tx.beta.2 DSP 1312 .+-.
535 738 .+-. 384 nitrates 1315 .+-. 507 1218 .+-. 445
[0280] DSP Lowers Plasma Cholesterol Level
[0281] Increased plasma cholesterol has been implicated in the
initiation of atherosclerosis. To prevent the formation of new
atherosclerotic lesions, the decrease of plasma cholesterol either
by modifying diets or drugs was recommended. It was examined
whether DSP decreases plasma cholesterol. DSP lowered the
cholesterol level by 0.3 mmol/L, which is statistically significant
at the P value 0.05. See Table 12 below.
13TABLE 12 DSP decreases plasma cholesterol Plasma cholesterol
(mmol/L) Pretreatment Posttreatment DSP 5.15 .+-. 0.16 4.84 .+-.
0.2
[0282] Number of patients: 80
[0283] Cardiotonic Pill's Effect on LPO and SOD in the Blood Serum
of Patients Suffering from Coronary Heart Disease
[0284] The method: In the treatment group, 24 patients, in
accordance with China Reference Diagnosis Standards for Coronary
Heart Disease amended in 1979, are administered with Cardiotonic
Pill, 10 pills/time, and 3 times/day. In the normal group, 20
healthy people do not receive any medical treatment.
[0285] The results: The level of LPO of the patients suffering from
coronary heart disease is clearly higher than that of the healthy
people, while the content of SOD is clearly lower (p<0.01).
After the patients are treated with Cardiotonic Pill, their LPO
evidently decreases (p<0.01), and their SOD evidently increases
(p<0.01). See Table 13 below.
14TABLE 13 A Comparison of the Contents of SOD and LPO in the
Normal and the Treatment Groups (x .+-. s) Groups Patients SOD
(ng/ml) LPO (nmol/ml) Normal 20 348 .+-. 106 4.64 .+-. 1.52 group
Treatment 24 Before 267 .+-. 76* 7.16 .+-. 1.48* group treatment
After 309 .+-. 87#. 4.68 .+-. 1.72## treatment Note: In comparison
with the normal group, *p < 0.05. In comparing with those of
pre-treatment, #p < 0.05, ##p < 0.01.
[0286] The conclusion: Chronic ischemia of cardiac muscles of
patients suffering from coronary heart disease and tissue anoxia
lead to the reduction of the activity of SOD, especially that of
extra cellular SOD, and the increase of oxygen free radicals, which
causes the elevation of LPO and consumption of SOD further. After
the patients are treated with Cardiotonic Pill, the level of LPO
decreases evidently, while the content of the SOD increases
obviously. This proves that Cardiotonic Pill has a strong action of
clearance on oxygen free radicals, which is also one of the
mechanisms to treat coronary heart disease.
[0287] The Effect of Cardiotonic Pill on the Activities of LPO and
Antioxidases in Treatment of Pulmonary Heart Disease
[0288] The method: The subjects: 48 patients suffering from
pulmonary heart disease are randomly divided into 3 groups. In the
normal group, 16 patients are treated with a complex of therapies,
such as anti-inflamatory therapy, antiasthma, oxygen inhalation,
and so on. In the Cardiotonic Pill group, 14 patients are treated
with Cardiotonic Pill, 10 pills/time, and 3 times/day. In the
Gantangzhi group, 18 patients are treated with the intravenous
drip--200 mg of Gantangzhi dissolved in 250 ml of 5% glucose
injection, 1 time/day, and 10 days/period.
[0289] The results: After treatment with Cardiotonic Pill, the
value of GSH-Px goes up, the value of LPO goes down, and,
therefore, GSH-Px/LPO goes up. In comparison with the normal
treatment group, there is a significant difference. See Table 14
below.
15TABLE 14 Indices before and after Treatments GSH-P.sub.x CAT SOD
LPO (U/mgHb) (U/gHb) (U/gHb) (nmol/ml) GSH-P.sub.x/LPO Healthy
people 140.6 .+-. 35.2 312.7 .+-. 58.1 5799.8 .+-. 948 4.2 .+-. 1.2
34.2 .+-. 8.7 group Normal Before 101.3 .+-. 23.6 300.4 .+-. 107.7
5740.5 .+-. 939.0 5.6 .+-. 1.9 20.4 .+-. 8.8 group treatment After
120.6 .+-. 20.6.sup.# 390 .+-. 184.3.sup.# 6076.8 .+-. 1091 4.3
.+-. 1.2.sup.## 31.3 .+-. 15.1.sup.## treatment Cardiotonic Before
108.8 .+-. 28.3 233.1 .+-. 70.2 5863.3 .+-. 1072.7 5.9 .+-. 2.0
18.5 .+-. 7.6 Pill group treatment After 158.2 .+-. 40.7.sup.##**
328.4 .+-. 78.5.sup.##* 5582.8 .+-. 1094.7.sup.#* 4.1 .+-.
1.6.sup.##** 36.4 .+-. 6.7.sup.##** treatment Note: Comparing those
before treatment with those after treatment, #p > 0.05, ##p <
0.05, *p > 0.05, **p < 0.05.
[0290] The conclusion: Cardiotonic Pill has the function of
antioxidation, and can lighten the lipid peroxidation reaction and
raise the ability of antioxidation of human body.
[0291] Treatment with Cardiotonic Pill for Essential
Hypertension
[0292] The method: (1) The choice of patients: Select those
patients suffering from Phase I or II essential hypertension, but
without secondary hypertension or cardiac, hepatic and renal
insufficiencies.
[0293] (2) The administration: Stop the patients from taking any
western and traditional Chinese medicines (except for hypotensors)
for two weeks, and then, in the third week, measure their blood
pressures and blood rheologyical indices and take down their
clinical manifestations. The double blind method is adopted. In the
Cardiotonic Pill group, the subjects take orally Cardiotonic Pill,
10 pills/time, and 3 times/day. In Compound Danshen Tablet group,
the subjects take orally Compound Danshen Tablet, 5 tablets/time,
and 3 times/day. The subjects in the control group take placebos,
and the period of treatment is six weeks.
[0294] The results: (1) Effect on the viscosity of whole blood.
After treatment, the viscosities of whole blood of patients in both
the Cardiotonic Pill group and the Compound Danshen Tablet group
drop remarkably, but the curves of the viscosities of whole blood
in the Cardiotonic Pill group at any shear rates go down more
sharply than those in the Compound Danshen Tablet group. See Table
15.
16TABLE 15 Effect of Cardiotonic Pill on the Viscosity of Whole
Blood (mPas, x .+-. s) Groups 3.83 s.sup.-1 28.3 s.sup.-1 192
s.sup.-1 Cardiotonic Before 18.27 .+-. 2.85 5.82 .+-. 0.93 4.54
.+-. 0.78 group treatment (30 After .sup. 11.79 .+-.
3.75**.sup.##&& .sup. 4.78 .+-. 0.84**.sup.##&&
.sup. 3.98 .+-. 0.65**.sup.##&& subjects) treatment
Compound Before 17.69 .+-. 1.96 5.86 .+-. 0.79 4.69 .+-. 0.54
Danshen treatment Tablet After 14.68 .+-.
3.41**.sup.&&.sup. .sup. 5.69 .+-. 0.81*.sup.& 4.42
.+-. 0.59**.sup.&&.sup. group treatment (30 subjects)
Control Before 17.65 .+-. 2.07 5.69 .+-. 0.79 4.75 .+-. 0.58 group
treatment (15 After 18.02 .+-. 2.32 5.71 .+-. 2.76 4.86 .+-. 0.65
subjects) treatment Note: In comparison with those of the same
group before treatment, *p < 0.05, **P < 0.01. Comparing with
those of the Cardiotonic Pill group after treatment, #p < 0.05,
##p < 0.01. Comparing with those of the control group after
treatment, &p < 0.05, &&p < 0.01.
[0295] (2) Effect on the deformation and the aggregation of
erythrocytes. After treatment, the deformation of erythrocytes in
Cardiotonic Pill group is markedly greater than that before
treatment, and the area and the index of aggregation are observably
smaller than those before treatment. And comparing with the
Compound Danshen Tablet group, the Cardiotonic Pill group declines
much faster (p<0.01). See Table 16.
17TABLE 16 Effect of Cardiotonic Pill on the Deformation and the
Aggregation of Erythrocytes (x .+-. s) Area of Index of Index of
Aggregation Groups Deformation Aggregation (integral) Cardiotonic
Before 0.4115 .+-. 0.0360 4.06 .+-. 0.39 841.12 .+-. 67.68 group
treatment (30 After 0.4274 .+-. 0.034*.sup.& 3.41 .+-.
0.36**.sup.#&& 683.52 .+-. 69.09**.sup.#&&
subjects) treatment Compound Before 0.4066 .+-. 0.0290 3.98 .+-.
0.34 806.90 .+-. 66.30 Danshen treatment Tablet After .sup. 0.4180
.+-. 0.0281*.sup.& 3.64 .+-. 0.39****.sup.&&.sup.
716.12 .+-. 84.29**.sup.& group treatment (30 subjects) Control
Before 0.4091 .+-. 0.0376 4.02 .+-. 0.41 812.52 .+-. 65.64 group
treatment (15 After 0.4001 .+-. 0.0381 4.01 .+-. 0.39 804.44 .+-.
68.06 subjects treatment Note: In comparison with those of the same
group before treatment, *p < 0.05, **p < 0.01. Comparing with
those of the Cardiotonic Pill group after treatment, #p < 0.05,
##p < 0.01. Comparing with those of the control group after
treatment, &p < 0.05, &&p < 0.01.
[0296] (3) Effect on Blood Pressure. After treatment, the systolic
pressures and the diastolic pressures of patients in both the
Cardiotonic Pill group and the Compound Danshen Tablet group drop
markedly (p<0.01), and there is no evident difference between
the two groups. See Table 17.
[0297] (4) Effect on symptoms of hypertension. The patients in both
the Cardiotonic Pill group and the Compound Danshen Tablet group
improve a lot in terms of such symptoms as headache, dizziness, and
numb extremities (p<0.01), but do not improve in insomnia. See
Table 18.
18TABLE 17 Effect of Cardiotonic Pill on Blood Pressure (mmHg, x
.+-. s) Systolic Groups pressure Diastolic pressure Cardiotonic
Before 155.00 .+-. 8.08 90.70 .+-. 7.93 group treatment (30
subjects) After 149.20 .+-. 8.89**&& 86.59 .+-.
8.30**&& treatment Compound Before 152.93 .+-. 9.59 92.59
.+-. 8.30 Danshen Tablet treatment group After .sup. 146.02 .+-.
10.20**&& 88.55 .+-. 7.22**&& (30 subjects)
treatment Control Before 154.06 .+-. 7.05 90.90 .+-. 9.10 group
treatment (15 subjects) After 152.08 .+-. 9.25 91.10 .+-. 8.70
treatment Note: In comparison with those of the same group before
treatment, **P < 0.01. Comparing with those of the control group
after treatment, &&p < 0.01.
[0298]
19TABLE 18 Effect of Cardiotonic Pill on Clinical Symptoms of
Hypertension (patients) Headache Dizziness Numb extremities
Insomnia Groups Yes No Yes No Yes No Yes No Cardiotonic Before 20
10 16 14 12 18 8 22 group treatment (30 subjects) After 7 23* 2 28*
3 27* 4 26 treatment Compound Before 22 8 17 13 10 20 6 24 Danshen
treatment Tablet After 15 15* 8 22* 3 27* 6 248 group treatment (30
subjects) Control Before 8 7 6 9 4 11 4 11 group treatment (15
subjects) After 7 8 5 10 3 12 2 13 treatment Note: In comparison
with those of the same group before treatment, *P < 0.01.
[0299] The conclusion: The Theological property of erythrocytes of
patients suffering from essential hypertension is clearly abnormal.
The deformation of erythrocytes debases clearly, while the
aggregation rises distinctly. The experiment shows that Cardiotonic
Pill has the functions of markedly reducing the viscosity of whole
blood and the index of and the area of aggregation of erythrocytes,
and greatly raising the ability of deformation of erythrocytes.
Cardiotonic Pill can also lower the blood pressure and improve
clinical symptoms of the patients. And thus, Cardiotonic Pill is of
great benefit to preventing or postponing the occurrence of
essential hypertension and cardio-cerebral syndrome.
[0300] Toxicity
[0301] DSP is safe and nontoxic. In China, over 5 million patients
have been treated with DSP without severe side effects. Mild side
effects, headache or dizziness, have been reported in a minor
portion of patients.
[0302] Summary of Clinical Studies
[0303] DSP is a new generation Chinese medicine for treating
coronary heart disease. Clinical studies demonstrate that DSP
alleviates as well as prevent angina by improving cardiac function,
reducing myocardial ischemia, inhibiting platelet activation thus
reducing blood stasis, and decreasing plasma cholesterol. The
therapeutic efficacy of DSP was superior to another form of Chinese
medicament Dan Shen tablets. DSP is as efficient as drugs used in
the USA. DSP is aleviate angina as efficiently as nitroglycerine,
prevents angina as efficiently as the long-acting nitrate isosorbid
dinitrate, and inhibits platelet aggregation as effectively as
aspirin. DSP is nontoxic: over 5 million people have been treated
without noticeable side effects in most cases.
[0304] Preclinical Studies
[0305] Preclinical studies reveal the mechanism by which DSP
prevent as well as alleviate angina.
[0306] DSP Alleviate Angina by Increasing Blood Flow.
[0307] Wistar rats, approximately 260 g, were anesthetized by
urethane, opened the chest, excise the heart, perfused in the
Langendorff mode at 37.degree. C. And constant coronary perfusion
pressure of 65 cm H.sub.2O.
[0308] After stabilized the heart rate, various amounts of DSP or
Danshen tablet were applied each time through lateral branch of
aorta cannula. Subsequently, the coronary flow and the heart rate
were measured. DSP increased coronary flow in a wide dosage.
Danshen tablet, on the other hand, increased coronary flow at a
narrow dosage. See Table 19 below.
20TABLE 19 DSP increases coronary flow Coronary flow Dose (mg/ml)
Pretreatment post-treatment None 7.0 .+-. 1.1 7.1 .+-. 0.97 DSP 5.8
7.2 .+-. 1.1 7.0 .+-. 1.4 290 6.7 .+-. 1.6 8.7 .+-. 1.4 580 6.7
.+-. 1.5 9.3 .+-. 2.9 DS Tablet 5.8 6.7 .+-. 1.4 7.1 .+-. 1.5 290
7.3 .+-. 1.7 9.1 .+-. 2.1 580 6.8 .+-. 1.4 7.1 .+-. 1.5
[0309] The effect of DSP and Danshen tablets on heart rate was
examined. Neither DSP nor Danshen tablet changes heart rate. See
Table 20 below.
21TABLE 20 DSP does not increase heart rate Heart rate Dose (mg/ml)
Pretreatment post-treatment None 194 .+-. 17 193 .+-. 12 DSP 5.8
180 .+-. 11 189 .+-. 9 290 188 .+-. 7 184 .+-. 8 580 173 .+-. 14
.sup. 167 .+-. 13 5.8 DS tablet 5.8 180 .+-. 11 189 .+-. 9 290 189
.+-. 16 183 .+-. 14 580 186 .+-. 23 171 .+-. 8
[0310] DSP Increases Coronary Flow by Relaxing Vascular Smooth
Muscle thus Dilating Vessels.
[0311] The effect of DSP on potassium-induced vasocontraction of
rabbit aortic strip was examined. DSP relaxed smooth muscle thus
dilating vessels significantly. Similar effects were observed in
the experiments using pig coronary artery rings.
[0312] DSP Inhibits Platelet Aggregation
[0313] The effect of DSP on platelet aggregation was examined.
Rabbit platelets were treated with DSP and aggregation was
examined. DSP inhibited platelet aggregation significantly. See
Table 21 below.
22TABLE 21 DSP inhibits platelet aggregation DSP (mg/ml) #animals
Aggregation ratio (%) inhibition (%) 0 6 6.7 .+-. 4.4 0 1.8 6 42.7
.+-. 2.5 8.3 .+-. 4.5 3.5 6 33.4 .+-. 3.4 23.6 .+-. 6.7* 7 6 25.3
.+-. 2.1 37.6 .+-. 5.9* 14 6 15.8 .+-. 3.0 69.0 .+-. 6.9*
[0314] Table 22 shows micronucleus rates in mice at Different Time
After treatment with the herbal composition of this invention (8400
mg/kg).
23TABLE 22 Polychromatic Micronucleus Micro-rates (%) Time (h) RBCs
Cells (x .+-. SD) 12 6,000 9 1.5 .+-. 0.8 24 6,000 11 1.8 .+-. 0.7
36 6,000 11 1.8 .+-. 1.2 48 6,000 11 1.8 .+-. 1.5 72 6,000 13 2.2
.+-. 0.7 Solvent 24 6,000 9 1.5 .+-. 1.4
[0315] Table 23 shows the micronuleus rates in Mice at 24 hrs after
DSP & CP Administration.
24TABLE 23 Polychromatic Micronucleus Micro-rates (%) Dose (mg/kg)
RBCs Cells (x .+-. SD) 8,400 6,000 12 2.0 .+-. 0.6 840 6,000 9 1.5
.+-. 1.0 84 6,000 11 1.8 .+-. 1.0 Solvent 6,000 9 1.5 .+-. 1.4 CP
(80 mg/kg) 6,000 138 23.0 .+-. 4.0* *Compare with solvent P <
0.01.
[0316] Table 24 shows assessment criteria for graded effectiveness
of tested drugs.
25TABLE 24 Very Parameters.backslash. high High Effects effect
Effect Effect No effect RBC No A little Marked Severe aggregation
status onset Time <90 90-180 180-300 >300 Micro-blood Better
Turn to Improved Deterior- flow status than normal ated normal
Duration (min) >15 15-10 10-5 <5
[0317] DSP Improves Microcirculation
[0318] The effect of DSP on microcirculation in Chinese hamsters
was examined. DSP improved microcirculation for 23 minutes within
111 minutes of buccal administration in all animals. See Table
below.
26TABLE 25 DSP improves microcirculation onset Time (min) Duration
(min) Effect rate (%) DSP 111 23 100
[0319] Table 26 shows the protective effect of DSP on the
myocardium induced by pituitrin in rats (second period).
27TABLE 26 (n = 8) After medication After Before pituitrin (40 s-15
Dosage medica- Before minutes) Number of Group (g/kg) tion
pituitrin rats with abnormal ECG Control Normal Normal 7 DSP 0.4
Normal Normal 3* 0.8 Normal Normal 1** 1.2 Normal Normal 1** DST
0.4 Normal Normal 4 0.8 Normal Normal 1** Compared with the
control. *p < 0.05; **p < 0.01.
[0320] Table 27 shows the inhibitory effect of DSP on myocardial
ischemia induced by pituitrin in rat. Table 27.
28TABLE 27 Group Dosage (g/kg) Inhibition (%) DSP 0.4 71.4* 0.8
85.7* 1.2 71.4* DST 0.4 42.8* 0.8 85.7* As compared with the
control. *p < 0.05.
[0321] Table 28 shows the protective effect of DSP on the
myocardial ischemia induced by pituitrin in rats (first
period).
29TABLE 28 (n = 8) Changes in T-ST of ECG- (lead II) in the first
period After medication After pituitrin (0-40 s.) Number of rats
with abnormal ECG Dosage Before Before elevated inverted Group
(g/kg) medication pituitrin T T Total Control -- Normal Normal 4 3
7 DSP 0.4 Normal Normal 3 0 3* 0.8 Normal Normal 1 1 2* 1.2 Normal
Normal 2 1 3* DST 0.4 Normal Normal 3 2 5 0.8 Normal Normal 1 1 2*
As compared with control. *P < 0.05.
[0322] Cardiotonic Pill's Action of Clearance on Oxygen Free
Radicals
[0323] The study of Cardiotonic Pill's action of clearance on
oxygen free radicals is carried out by using electron paramagnetic
resonance (EPR) and spin trapping, with superoxide anions and
hydroxy radicals produced by using the xanthine-xanthine oxidase
system and the H.sub.2O.sub.2-Fe.sup.2+ system respectively.
[0324] The method: (1) Production of hydroxy radicals. Set up a
test model according to the Fenton Principle. Mix up
H.sub.2O.sub.2, ferrisulphas and DMPO
(5,5-dimethyl-pyrroline-l-oxide), and then carry out the EPR
testing. The resulting signals serve as the control. Add
Cardiotonic Pill in the treatment group.
[0325] (2) Production of superoxide anions. Set up a test model
based on the xanthine-xanthine oxidase reaction. Mix up xanthine,
Dietrylene triamine Pentacetic acid, DMPO and xanthine oxidase, and
then carry out the EPR testing. The resulting signals serve as the
control. Add Cardiotonic Pill in the treatment group.
[0326] Ten samples for each of the four groups are tested, and the
results are expressed in terms of the average. T-test is applied in
the statistical analysis.
[0327] The Results: (1) Cardiotonic Pill's action of clearance on
hydroxy radicals produced by the H202-Fe2+system. An adduct DMPO-OH
will be generated when a hydroxy radical is captured by a DMPO. The
peak value of the adducts in the control group is 11.8.+-.0.6
relative units, while that in the Cardiotonic Pill group is
4.1.+-.0.5 relative units. There is a significant difference
between them (p<0.01), and the clearance rate of Cardiotonic
Pill is over 65%.
[0328] (2) Cardiotonic Pill's action of clearance on superoxide
anions produced by the xanthine-xanthine oxidase system. An adduct
DMPO-OOH will be generated when a superoxide anion is captured by a
DMPO. The peak value of the adducts in the control group is
10.6.+-.0.67 relative units, while the spectral signals in the
Cardiotonic Pill group disappear completely. In comparison with the
control group, there is a significant difference (p<0.01), and
the clearance rate of Cardiotonic Pill is 100%.
[0329] The above experiments show that Cardiotonic Pill has an
effective action of clearance on superoxide anions produced by the
xanthine-xanthine oxidase system and hydroxy radicals produced by
the H202-Fe2+system.
[0330] Cardiotonic Pill's Effect on Free Radicals of Cerebral
Ischemia Reinfusion Injury Tissue of Rats
[0331] The method: Take 30 SD rats, and randomly divide them into 3
groups, which are the feigned operation group (An operation is
performed, but the blood vessels and nerves are not ligated), the
cerebral ischemia reinfusion model group and the Cardiotonic Pill
group (4 g/kg). After the 3-day continuous intraperitoneal (Ip)
administration, and two hours after the administration on the third
day, the rats are anaesthetized with the 20% Ethylurethanm and
their conducting arteries in both sides of their necks and vagus
nerves are separated and ligated. After a 30-minute reinfusion, cut
off their heads and get their brains. Take about 500 mg of cortical
tissues of their left-brains and hippocampus tissues in both sides,
and put them into the liquid nitrogen for homogenization. After
they are made into a homogenate with freezing physiological saline,
centrifugate the homogenate. Take the supernatant and determine the
activities of CAT and SOD and the contents of MAD and GSH.
[0332] The results: See Table 29. (1) Cardiotonic Pill's effect on
the activity of CAT and the content GSH of brain tissues. The
activities of CAT of brain cortex and hippocampus tissues and the
content of GSH of the brain cortex in the cerebral ischemia
reinfusion model group are much lower than those in the feigned
operation group. Both the activity of CAT of hippocampus tissues
and the content of GSH of the brain cortex in the Cardiotonic Pill
group are significantly greater than those in the model group.
30TABLE 29 The Activities of CAT and SOD and the Contents of MDA
and GSH of Brain Tissues of the Rats (mPas, x .+-. s) (n = 10) CAT
Activity GCH SOD Activity MDA (U/mg Protein) (.mu.mol/mg Protein)
(U/mg Protein) (nmol/mg Protein) Groups Brain Cortex Hippocampus
Brain Cortex Hippocampus Brain Cortex Hippocampus Brain Cortex
Hippocampus Feigned 2.94 .+-. 0.17 2.78 .+-. 0.14 18.49 .+-. 0.70
16.87 .+-. 0.92 14.24 .+-. 0.90 20.34 .+-. 0.74 0.502 .+-. 0.054
1.084 .+-. 0.117 Operation Group Model 2.17 .+-. 0.24.sup.8 1.97
.+-. 0.23.sup.8 14.76 .+-. 1.12.sup.8 13.80 .+-. 0.74 10.44 .+-.
0.79.sup.8 18.18 .+-. 0.62.sup.8 0.718 .+-. 0.070.sup.8 1.449 .+-.
0.140.sup.8 Group Cardio- 2.55 .+-. 0.35 2.79 .+-. 0.21.sup.3 17.14
.+-. 0.76 15.76 .+-. 1.18.sup.3 13.31 .+-. 0.77.sup.3 20.59 .+-.
0.59.sup.3 0.483 .+-. 0.065.sup.3 1.069 .+-. 0.131.sup.3 tonic Pill
Group Note: In comparison with the feigned operation group, *p <
0.05; in comparison with the model group, #p < 0.05
[0333] (2) Cardiotonic Pill's effect on the activity of SOD and the
content MDA of brain tissues. The activity of SOD of brain tissues
in the model group is significantly lower than that in the feigned
operation group, while the content of MDA is significantly higher.
The activities of SOD of brain cortex and hippocampus tissues in
the Cardiotonic Pill group increase significantly, while the
content of MDA decreases significantly.
[0334] The conclusion: After cerebral ischemia reinfusion, the
content of MDA in the brain tissues increases, while the content of
GSH decreases. The activities of CAT and SOD, two important enzymes
for clearing oxygen free radicals in the tissues, decrease
significantly, which shows that during the course of cerebral
ischemia reinfusion, a great lot of oxygen free radicals occur due
to the failure of the function of the free radical clearance
system. This leads to the lipid peroxidation, and then leads to the
brain injury. Cardiotonic Pill can decrease the contents of MDA in
the brain cortex and hippocampus tissues of reinfused rats and
increase the content of GSH and the activities of CAT and SOD
greatly, which shows that Cardiotonic Pill has the functions of
markedly restraining the reactions of oxygen free radicals,
controlling the lipid peroxidation and protecting damaged brain
cells caused by ischemia reinfusion.
[0335] The Antioxidation of Cardiotonic Pill in Chronic Hepatic
Injury
[0336] The method: The CCL4-high-fat-low-protein induced mild
chronic hepatic injury model of the Wister rat is adopted. In the
Cardiotonic Pill group, perfuse Cardiotonic Pill into the rats'
stomachs at the dose of 4 g/kg, while in the normal and the model
groups, perfuse the same amount of physiological saline. The
activity of SOD is determined by using the xanthine oxidase method,
while the content of the MDA is determined by using the improved
thiobarbituric acid method.
[0337] The results: See Table 30. Comparing the model group with
the normal group, the activity of SOD degrades, while that of MDA
increases. In the Cardiotonic Pill group, however, the activity of
SOD increases, while that of MDA degrades, making the Cardiotonic
Pill group go back to the normal.
31TABLE 30 The Activities of SOD and the Contents of MDA in Chronic
Hepatic Injury SOD MDA Groups Rats (NU/mg.pr) (nM/mg.pr) Normal
group 12 1.717 .+-. 0.521 15.21 .+-. 4.35 Model group 12 1.326 .+-.
0.3218 19.39 .+-. 4.62* Cardiotonic 11 1.710 .+-. 0.415# 15.16 .+-.
4.29# Pill group Note: In comparison with the normal group, *p <
0.05. In comparison with the model group, #p < 0.05
[0338] The conclusion: MDA is a major degradation product of the
lipid peroxidation. MDA can badly damage the structure of the cell
membrane, and then hepatic cells. SOD is a scavenger of super-oxide
anion free radicals, and it can restrain the lipid peroxidation
caused by free radicals. Cardiotonic Pill can significantly
increase the activity of SOD and decrease the content of MDA, which
will degrade the level of the lipid peroxidation and lighten the
hepatic injury.
[0339] DSP is not Mutagenic
[0340] It was examined whether DSP is mutagenic in the Ames assay.
DSP was not mutagenic. See Table 31 below.
32TABLE 31 The mutagenicity of DSP (Ames test) colony number per
dish S9 TA97 Ta98 TA100 TA102 DSP - 0.0 - 141 .+-. 13 36 .+-. 3 161
.+-. 21 303 .+-. 44 0.5 - 140 .+-. 17 35 .+-. 2 148 .+-. 21 288
.+-. 15 5 - 136 .+-. 14 34 .+-. 4 154 .+-. 26 280 .+-. 16 50 - 133
.+-. 20 33 .+-. 5 142 .+-. 25 292 .+-. 37 500 - 109 .+-. 15 34 .+-.
3 154 .+-. 16 311 .+-. 32 5000 - 67 .+-. 8* 30 .+-. 4 149 .+-. 27
298 .+-. 32 0.0 + 141 .+-. 13 44 .+-. 6 176 .+-. 19 296 .+-. 39 0.5
+ 148 .+-. 13 42 .+-. 9 161 .+-. 27 296 .+-. 37 5.0 + 152 .+-. 11
44 .+-. 7 161 .+-. 16 292 .+-. 38 50.0 + 140 .+-. 18 37 .+-. 6 166
.+-. 9 307 .+-. 55 500.0 + 135 .+-. 21 42 .+-. 7 152 .+-. 22 287
.+-. 16 5000.0 + 119 .+-. 17 38 .+-. 7 162 .+-. 17 363 .+-. 57
Dexon 50 - 2155 .+-. 814 952 .+-. 187 831 .+-. 114 1510 .+-. 211
2-AF 40 - 125 .+-. 18 38 .+-. 3* 161 .+-. 16 + 1404 .+-. 644* 1598
.+-. 124 1222 .+-. 309 DAN 100 - 364 .+-. 50 + 943 .+-. 102*
[0341] Production of Crude Drugs
[0342] 1. Dan shen
[0343] (1) Quality Control
[0344] Crude drug Dan Shen was sampled from production arias
throughout China. Chemical analysis was conducted on those samples
from different bases for their chief components. The results showed
that the quality of Dan Shen from an aria named Shangluo was the
best of all and it proved that the climate of Shangluo is most
suitable for the growth of Dan Shen. The active ingredients of Dan
Shen such as tanshinone and salvianic acid A. were approved the
best in quantity.
[0345] (2) Topography
[0346] Shangluo is geographically located at the East Longitude
108.degree.34'20".about.111.degree.1'25" and North Altitude
33.degree.2'30".about.34.degree.24'40" with an average sea level of
900 meters. The region is an area with low and median high
mountains and is free of pollutions. The unpolluted clean air
circumstance makes it ideal for the growth of drug plants.
[0347] (3) Climate
[0348] It is warm and semi-humid in climate, typical for the
mountainous areas of transitional zone from the subtropics to the
temperate. Affected by the South-eastern monsoons, it has obvious
divisions for seasons and a great amount of rain. The precipitation
of rainfall of the year in this area is estimated at 733.9-899 mm.
The sunshine period is around 1874.1-2185 hours a year, with an
annual sun irridiance of 119.57-124.36 kilocalories/cm.sup.2. The
temperature varies from 18.degree. C.-40.8.degree. C. A frost-free
period lasts 198-218 days of the year.
[0349] (4) Soil
[0350] 80% of the soil in Shangluo is arenaceous, most of the
arable land comprises of neutral and alkalescent soil with a pH
value of 6.5-8. Within 0-20 cm of the tillage layer, the soil
nutrients consist of the following: 1.36% organic matter; 0.085%
nitrogen; 18 ppm fast-effective phosphor; 136 ppm fast-effective
potassium; and 60 ppm alkaline-hydrolyzed nitrogen. Heavy metals
and other toxic matters contained in the soil do not exceed the
agricultural standards set by the country. The region is rich in
plants and animals. Local farmers use organic fertilizers.
[0351] (5) Heavy Metals:
[0352] The eight metals, including Lead, cadmium, mercury, arsenic,
etc., the pesticide residues, air and water all meet the country
environment standards.
[0353] (6) Standardization
[0354] The planting and plowing of Dan Shen follow the standard of
Good Agriculture Practice (GAP). Technological know-how relevant to
the growing of Dan Shen is compiled into a booklets and distributed
among the Dan Shen growers in the base. During the planting
seasons, technicians are sent to the fields to give growers
training on the spot and offer technical support, so as to
standardize the planting of Dan Shen on a large plantation-like
scale.
[0355] (7) The Shangluo production base had bred and cultivated 20
different breeds of Dan Shen. Different Dan Shens were observed and
compared in their growth situations, yield, appearance and chemical
components for three years. The best breeds in quality chosen for
large-scale plantation.
[0356] (8) Tissue cultivation and clone technology are adopted in
the Dan Shen cultivation to accelerate the procedure and shorten
the circle of growth.
[0357] (9) After a 30-day period of test-tube planting, an enlarged
reproduction procedure is taken. It lasts 40 days before the root
period. The root period will takes another 10 days that is for the
plants to generate and enrich their roots. The rate of rooting
usually reaches 90% or above. The plant can then be transferred to
the nursery, where advanced spray irrigation device and conditions
are controlled by computer technology. The plants can be
transplanted to the outside field after a month cultivation in the
nursery.
[0358] (10) According to the experts, the cultivated Dan Shen from
our product base are not only in high quality but also productive
for their productive roots (50% more in root weight than those from
other areas), and high chemical composition (70% higher in active
drug ingredients than samples from other places).
[0359] 2. Natural Borneol
[0360] (1) Growth Conditions
[0361] The growth areas of natural Borneol are Xinhuang county of
Hunan province, China, a region with mid-height hills at a sea
level of 300-600 m. 60% of the area is covered by forest. The land
consists of yellow and red sand soil with pH 5-6. No air or water
pollutions are found within the region.
[0362] (2) Biological Characteristics of the Tree
[0363] Extremely strong growth capability, it grows in brushwood
field, 300-400 trees per mu (equal to 666.7 m.sup.2); Parts above
branch leaves are collected; net gain is 1000 kg per mu.
[0364] (3) Reproduction and Transplant
[0365] Use grafting and cuttage technology for reproduction. The
Plant grows in the nursery garden during the first year and is
transplanted to the filed in the spring of the second year. The
filed need to be fertilized and scarified periodically.
[0366] (4) The plant may grow up to 30 cm in height and 80-100 cm
for the largest diameter. It contains natural Camphor in different
parts of the plant: leafs, branches, trunk and roots. Among all,
the leaves contain the most of Camphor content.
[0367] (5) The Borneol-type Camphor from Xinghuang is one of the
natural variation of Cirnamonium glandullferm (wall) Noes. The
Camphors trees vary in contents of Camphor and Borneol, Some are
low in Borneol, high in Camphor while others high in Borneol and
low in Camphor. Through an assay with large amount of samples and
many HPLC analyses, we finally choose a kind of Camphor trees that
contains over 80% Borneol with less impurity.
[0368] 3. Radix Notoginseng
[0369] a. Seeds of the Plant
[0370] (1) Determination of Radix Notoginseng
[0371] With the PCR reaction for molecular mass marking, Radix
Notoginseng can be stained observed, Radix Notoginseng has its
characteristic DNA fingerprinting.
[0372] (2) Shape and properties
[0373] The Radix Notoginseng seed has a round, circular body. For
seeds of different growth period, Radix Notoginseng has 2-year or
3-year seeds. The 2-year seed is 0.45-0.55 cm in diameter and
95-103 grams in weight for its dried grain. The 3-year seeds is
0.54-0.65 cm in diameter and 98-109 grams in weight for its dried
grain.
[0374] (3) Suitable Temperature for Seed Sprouting
[0375] The appropriate temperature for seed sprouting is
10-30.degree. C., the ideal temperature is 15-20.degree. C.
[0376] (4) Water Content
[0377] The amount of water contained should be 60-70%, if water
content is below 20% for a long period of time, the seeds will lose
vivacity.
[0378] (5) Dormancy
[0379] The seeds have a tendency to go through dormancy for 45-60
days after collection.
[0380] (6) Life Span
[0381] The seeds have a life span of 15 days in natural state after
they are collected.
[0382] (7) Requirements for Storage of Seed
[0383] Seeds for storage should be collected from the plants that
grow more than two years and the tree should be growing
prosperously for parts above the earth and pest-free. It is
recommended that seeds be collected from three-year plants.
[0384] (8) Management for the Seed Reservation Field
[0385] Seed reservation field should be better managed than the
regular production fields, contaminated plants should be disposed
of at all times, pests should not come in contact with the buds
under any circumstances. During period of sprouting of buds and
leafs, 3000 ppm of YunDa-120 and 400 times solution of Yang Kang
biological fertilizer should be sprayed twice. And, during
florescence and fruit period, Phytokinin is sprayed.
[0386] (9) Harvest Period of the Seed
[0387] The harvest period of Radix Notoginseng seed is from the end
of October to the beginning of December.
[0388] (10) Methods for Collection of Seeds
[0389] The collection of the seeds is decided dependant upon the
levels of maturity of the seeds. The seeds from trees that grow
stronger will be collected and stored separately. The base strictly
prohibits collection of immature plants.
[0390] (11) Processing
[0391] Plants are washed immediately after collection while pulps
and blighted seeds are picked out. Dry the plants in the sun after
washing.
[0392] (12) Storage
[0393] Use 300 times solution of 58% metalaxyl manganous zinc
dissolvable liquid to treat Radix Notoginseng seeds for 30 minutes.
let the surface of the seeds become dry, and store the seeds with
wet sand containing 20% water. It is a crucial step for the
process.
[0394] (13) Packaging
[0395] Final products are packaged in uncontaminated containers,
There should be signs that indicate the date of collection,
processing, and the product batch number.
[0396] (14) Transporting
[0397] Clean, waterproof and ventilated transportation vehicles
instruments should be used for transportation in order to prevent
the product being contaminated with toxic matters. If it takes more
than 8 hours for transportation, the product seed should be with
the wet sand.
[0398] (15) Test for Vitality of the Seeds
[0399] Use the TTC methods: weigh accurately 1 g of tetrazolium
powder and dissolve it in 1000 mL of distilled water to make up the
solution of 0.1% TTC. Immerse the sample into the solution and keep
it for 24 hours, take it out and cut it into half and place
one-half into a culture disk. Use the prepared 0.1% TTC to dye the
sample for 30 minutes. The vitality of the seeds can be determined
by the color of the seeds
[0400] (16) Inspection of Pests
[0401] i. Observe the seed with human eyes while placing 500-1000
sample pellets on a white sheet of paper or glass. If unusual spots
or pests appear on the surface of the sample, the contamination can
be decided. Contaminated samples should be taken apart and be
identified for its level of contamination.
[0402] ii. Cutting and Inspect: use a scalpel to cut and open 2
sample sets each contain 100 seeds. Calculate the number of
contaminated seeds to determine the level of contamination.
[0403] iii. Smell to inspect samples: place them in hand and detect
them by nose for any moldy odor. Or simply leave sample in a cup
containing heated water (60-70.degree. C.), and covered for 2-3
minutes, pour out the water and smell the seeds. The seeds should
send forth a delicate fragrance, if not, it is probably
contaminated.
[0404] (17) Color Inspection
[0405] An uncontaminated seed should have light yellow and white
color.
[0406] (18) Microscopic Inspection
[0407] Pick out 5 test sample sets by random (each sample contains
no less than 50 ceeds), place the samples in a culture disk for 24
hours. Observe them under a microscope to detect them for any
pathogenic bacteria, if so, calculate the level of
contamination.
[0408] b. Seedling of the Plant
[0409] (1) Temperature for Sprouting
[0410] The temperature for Radix Notoginseng's sprouting is
1-20.degree. C., the ideal temperature is 15.degree. C.
[0411] (2) Water Content
[0412] The water content of the soil used for seedling plant is
20-25%.
[0413] (3) Storage
[0414] The development of Radix Notoginseng from resting bud to
sprouting requires 90 days of dormancy period. 100 ppm of
gibberellin can help shorten the Radix Notoginseng's dormancy
period.
[0415] (4) Refining
[0416] Radix Notoginseng's refinery period is from the beginning of
December to the end of January. While refining, the roots should be
handled with care. Plant immediately after refinery.
[0417] (5) Transportation
[0418] Radix Notoginseng cannot be transported over long distance,
otherwise it will be damaged. If unavoidable, Radix Notoginseng
should be placed in a ventilated container with soil, without
direct exposure to sunlight.
[0419] (6) Quality Inspection
[0420] i. For weight of each unit, choose 300-500 seedling plant as
samples, put each 100 seedling plants in a group, weigh them on the
balance and calculate the unit weight.
[0421] ii. For pesticide inspection: set up four groups of samples
each contains 100 seedling plants. Place samples on a glass disk
and observe the samples with human eyes or 5-10 times magnifying
lens to check for their pesticide.
[0422] iii. Set up four groups of sample each contains 100 plants,
slice the samples for an observation under the microscope.
[0423] c. Culture of the Seedling
[0424] (1) Field Condition
[0425] Radix Notoginseng seedling plants are cultured in the
best-conditioned areas. The base uses centered culture and
large-scaled cultural method.
[0426] (2) Environment
[0427] The area is totally free of pollutions. The air quality is
above level 2 of GB 3059-96 standard.
[0428] (3) Water Resources
[0429] The water resources consist of rainwater, underground water,
and natural running water. Water quality in the area is monitored
with the GB 5084-92 standard.
[0430] (4) Soil
[0431] Radix Notoginseng cannot be planted in oozy soil, the amount
of heavy metals in the soil chosen for Radix Notoginseng must be
within relevant country standard.
[0432] (5) Ideal Soil
[0433] For a good result expected, we choose acidic soil (pH
5.5-7.0) with a slope no more than 15.degree.. A level no more than
1600 m above the sea should be with 8-12% of sunshine, and level
more than 1600 m above sea level should be 10-20% of sunshine.
[0434] (6) Temperature
[0435] During sprout period the atmospheric temperature should be
at 20-25.degree. C., and the earth temperature is at 10-15.degree.
C. During bearing period is the best atmospheric temperature that
is 20-25.degree. C., and the best soil temperature that is
15-20.degree. C.
[0436] (7) Water Content
[0437] Water content of soil should be at 25-30%.
[0438] (8) Soil Preparation
[0439] Soil plotting should be repeated for 3 times before
planting, and soil be exposed under sunlight, it helps to
exterminate bacteria substance in the soil.
[0440] (9) Handle with Soil
[0441] For prevention of root damage, 75-100 g of lime is used each
square meter before transplanting.
[0442] (10) Construction and Management of Shade
[0443] The shade is 1.8 m above ground with a 2 m deep trench below
the ground. Sunlight penetration is best at 8-10% if in area of no
more than 1600 m above sea level, or 10-15% if it is more than 1600
m. The ground should be flat; deep layer of the earth should be
lose; while the surface level of the earth should be rigid.
Planting season is best at the end of December to the end of
January. Before planting, the seeds should be immersed in 58%
metalaxylic zinc (500-800.times.) or 1.5% antimycin (200 ppm) for
30-50 minutes and dip out to let dry. This is to protect the plant
from diseases (Coated seeds do not have to undergo the above
procedures) Density of planting is to be 4.times.5 cm or 5.times.5
cm, with 100-200 thousand seeds per mu of land. Use special tools
to create a shallow gutter and use machine or hands to seed and
plant. Seeds are covered with fine soil completely.
[0444] After all, fertilizing, watering and weeding tasks are
performed. Weeds should be eliminated all the time. If the shade is
broken, it should be repaired immediately and ensured the correct
penetration of sunlight. Natural fertilizers including poultry
waste, stove dust, and bone dust (human waste should not apply)
[0445] d. Radix Notoginseng Cultivation
[0446] (1) Topology
[0447] The ground is best be with a moderate slope under 15.degree.
and a good exposure to sunshine.
[0448] (2) Soil Texture
[0449] It is the best if the ground is deeply seated with loose and
sand soil.
[0450] (3) Soil pH Should be at 5.5-7.
[0451] (4) Pre-Planted Crops
[0452] Corns, wheat, and beans are pre-planted in new fields in
avoid of soil destruction.
[0453] (5) Sea Level
[0454] 1400-1800 m above sea level near an altitude of 23.50 is the
location of the most suitable Radix Notoginseng area for
cultivation.
[0455] (6) Sunshine
[0456] Radix Notoginseng is a kind of plant that requires only
8-20% of sunshine. The amount of sunshine should be varied
increased in respect to different period of its growth. However,
too much sunshine exposure will result in stagnant plants.
[0457] (7) Water Content
[0458] The water content within the soil should be at 25-30%.
[0459] (8) Fertilizer
[0460] Organic fertilizers are used along with compound
fertilizers, micronutrient fertilizers, or trace-element
fertilizers.
[0461] (9) Temperature
[0462] The average temperature is estimated at 15-18.degree. C.
during the year in the Radix Notoginseng area. During sprout
period, atmospheric temperature should be, the most suitable, at
20-25.degree. C., and soil temperature 15.degree. C. During
nutrient development and blooming period, temperature is better be
kept at 25.degree. C. If the temperature is below 15.degree. C.,
florescence will be affected.
[0463] (10) Filed Division
[0464] Before cultivation, the field should be ploughed and
loosened 3 times until its structure becomes powderized.
[0465] (11) Soil Management
[0466] Before sowing and transplanting, apply 75-100 g of quick
lime to soil for sterilization purposes.
[0467] (12) Standards of the Bed
[0468] Flat ground soil bed of 20-25 cm in height, at slope area it
should be 15-20 cm. The width of the bed is between 120 and 140 cm
in a shape of a tile. The soil at the bottom of the base should be
loose and that on the top should be solid, that is for better
penetration.
[0469] (13) Seed Soaking
[0470] During transplanting, soak seed for 30-50 minutes in 58%
metalaxyl (500-800.times.) and then let dry, this will prevent
plant from diseases and eliminate pests.
[0471] (14) Density of Planting
[0472] Keep a distance of 10.times.12.5 cm-10.times.15 cm in plant
density. That is 26-32 thousand plants every mu.
[0473] (15) Methods for Transplanting
[0474] Seedlings are planted facing the same direction for
management purposes. In case of slope grounds, seedlings are
planted from low end to the high ground. The first row of seedlings
is facing up while the second row faces down. Buds are also to face
upward, and the bottom is to face inward.
[0475] (16) Covering of Soil
[0476] Use powdered, loose, and moistures soil to cover the
seedlings completely, without exposing the roots or the buds.
[0477] (17) Fertilization
[0478] Use poultry waste, stove ash, bone ash, Calcium Magnesium
Phosphate, etc as specialized fertilizer.
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[0522] Second Series of Experiments
[0523] This invention involves a medication which can prevent and
cure coronary heart disease with angina pectoris, the methods of
manufacture and other usages of the medication. The medication, Dan
Shen Pill (DSP), is made from a variety of Chinese herbs using a
series of standardized procedures.
[0524] DSP is an improvement on Dan Shen Tablet (DST) (recorded in
Pharmacopoeia of the People's Republic of China in Edition, 1977,
1985, 1995, and 2000), but there are significant differences
between DSP and DST: proportions in their formulas, manufacturing
techniques and their clinical results.
[0525] The number of patients with cardiovascular or
cerebrovascular diseases increases along with higher living
standards (better supply of foods), the worldwide aging problem,
and young adult's involvement. It has become the second most-common
diseases worldwide threatening the health of human beings. Angina
pectoris is caused by insufficient blood and oxygen supply to the
heart. The main clinical symptom is chest pain. It is caused by
atherosclerosis or spasms of coronary artery in about 90% of the
angina pectoris patients.
[0526] The major treatments for angina pectoris are vessel
dilation, lowering of blood viscosity, anti-aggregation of
platelets and anti-coagulation. The traditional medicines used are
nitrates, beta-adrenoceptor blocking drugs and calcium-channel
blocking drugs. However, all these drugs have many side effects
which make them unsuitable for long-term use. For example, patients
experience a swelling sensation in their heads, faster heartbeat
and even coma after taking glyceryl trinitrate.
[0527] Although there are many Chinese herbal medicines used for
treating angina pectoris, fewer people use them nowadays. DST or
capsules are being sold in the market, but their manufacturing
techniques are old, the efficacy is low and there are no quality
standards. DST is taken orally and absorbed in the gastrointestinal
tract, where it is absorbed into blood vessels after processing in
the liver. The bioavailability is low, and the absorption speed is
low, which is not suitable for the emergency treatment of patients
with angina pectoris.
[0528] In order to compensate for the inadequacy of the above
technology, the drug disclosed in this invention was developed to
provide high efficacy for the prevention and cure of coronary heart
disease with angina pectoris.
[0529] The other aims of this invention are to provide other
medical uses in addition to the prevention and cure of coronary
heart disease, the proportion of herb composition and the method of
manufacturing this drug.
[0530] This drug is prescribed according to traditional Chinese
medical theory and modern pharmaceutical research. Chinese medical
theories state that chest pains are caused by blood stagnation in
the arteries, lack of blood supply and blood nourishment to the
heart. After pharmaceutical experimentation and clinical
observation, Radix Silviae Miltiorrhizae is used as the main
ingredient. Panax Notoginseng and borneol are the co-ingredients
which eliminate blood stagnation, thereby preventing and curing
coronary heart disease with angina pectoris. The above ingredients
are grouped and mixed with other inactive ingredients to make
DSP.
[0531] DSP can prevent and cure coronary heart disease with angina
pectoris by the following mechanisms:
[0532] Increase by the blood flow to the ischemic area: dilating
the coronary artery, increasing blood flow to the coronary artery,
and activating peripheral circulation to improve blood supply to
the ischemic area.
[0533] Removing of free radicals: removing free radicals released
by hypoxia and ischemia, reducing damage to myocardial muscles and
increasing myocardial ATP content to protect myocardial muscles.
Preventing the aggregation of platelets: controlling the release of
platelet factors, preventing platelet aggregation and increasing
the PGI2/TXA2 ratio to prevent coagulation and thrombosis.
[0534] Lowering of blood cholesterol: controlling the biosynthesis
of cholesterol and lowering the synthesis of TG and LDL.
[0535] Xin, Zhiqiang, et al. (1996) reported in the Chinese Journal
of Integrated and Western Medicine on the effects of Radix Siliviae
Miltiorrhizae on 24 patients with coronary heart disease and
observed the changes in their LPO and SOD contents before and after
treatment. Having compared these 24 patients with 20 healthy
people, it was found that patients with coronary heart disease had
a higher LPO content than normal healthy people and a lower SOD
content. After undergoing treatment, patients' LPO level dropped
significantly, while SOD level rose. Conclusions are that Radix
Silviae Miltiorrhizae can lower LPO, increase SOD activity,
decrease platelet aggregation, improve myocardial ischemia, and
protect the myocardial membrane.
[0536] Chang, yingzi, et al. (1991) reported in the Chinese Journal
of Pathology and Physiology on an experiment in which
FeSO4/Ascorbic was introduced to monitor the damaging effects of
oxygen-free radicals on rod-shaped H+-ATPase of rat myocardial
muscles. The results showed that FeSO4/Ascorbic can lower the
hydrolysis ability of the rod-shaped H+-ATPase. Moreover, Danshensu
has an obvious protective function: It can prevent the decrease of
the hydrolysis ability of rod-shaped H+-ATPase and shows a
concentration-dependent relationship and saturation effect.
[0537] Zheng, Ruoxuan, et al. (1992) reported in the Chinese
Journal of Integrated and Western Medicine on an experiement in
which water extracted Radix Silviae Miltiorrhizae (5 g raw
medicine/k.sub.g), was injected into rats. The water extraction
prevents acute myocardial ischemia caused by blockage of the
coronary artery. The, increased ECG section ST caused by myocardial
ischemia after treatment was much lower than that in the control
group. The area of left ventricular ischemia is minimized and the
animal's chance of survival is increased.
[0538] Han, Chang, et al. (1991) reported in the Journal of Chinese
Pathology and Physiology on an experiment in which the rabbits are
anesthetized, chests opened, coronary artery tied to create an
acute myocardial ischemia model, and then tested the change in
local blood flow and myocardial lipid peroxidation content, an ECG
was conducted while the animal was observed. DSP was injected as a
protective agent. The results showed that myocardial lipid
peroxidation content increases along with a longer duration of
ischemia. When the heart is reperfused with blood for 30 minutes
after a 60 minute ischemia, the lipid peroxidation content still
increases continually, which is obviously higher than that of a
60-mins control group, but similar to that of a 90-mins control
group. The blood flow of local tissue in the ischemia area
recovered 53.2% after reperfusion, while in the DSP-protected
group, the ischemia area decreased 56% after reperfusion
(P<0.005). Blood flow recovery in local tissue increased 32%
(P<0.001).
[0539] Jiang, Wende, et al. (1982) reported in Journal of Shanghai
the First Medicine College on an experiment which compared DSP,
DS-781, PCAD and persantin using four different tests. Results:
extraction of Radix Silviae Miltiorrhizae can significantly
lengthen the toleration time for hypoxia and protect ischemic EC
change in mice. It can also prevent the lowering of LVPSP and
rising of LVEDP. In contrast, PCAD lowers LVPSP and raises LVEDP
more obviously. Vein injection to the persantin group can lower
LVPSP but has no effect on LVEDP. The minimization of the area of
myocardio infarction by Radix Silviae Miltiorrhizae extraction is
the most significant.
[0540] Wu, Huaizhu, et al. (1994) reported in the Chinese Journal
of Bloodology that the active principle of Radix Silviae
Miltiorrhizae can suppress ADP or collagen-induced platelet ATP
release and release relative aggregation. Inhibition shows a
volume-effect relationship. 0.01-0.08 mmol/L764-3 can prolong the
lag period in which arachidonic acid guides the activation of
bloodplatelets. When concentration is increased to 0.08 mmol/L,
coagulation of blood platelets and the release of ATP can be fully
controlled. Aequorin-loaded platelet suspension analysis discovered
that 764-3 can obviously inhibit the increase in plasma Ca++
concentration and inhibit Ca++ internal reflux and the activity of
internal Ca++. 764-3 can significantly inhibit the production of
AA-induced platelet TXB2. Conclusions: 764-3 may suppress the
metabolism of AA blood platelets.
[0541] Sun, Ximing reported in Chinese Traditional and Herbal Drugs
that research is being conducted on the pharmaceutical effects of
Danshensu using the cell model. It has been discovered that
Danshensu can lower the biosynthesis of cholesterol and obviously
lower migration ratio of electrophoresis. The MDA content in
oxidized lipoproteins decrease and the toxicity of oxidized
lipoprotein is also reduced. It shows that Danshensu can prevent
atherosclerosis.
[0542] Shi, Lin analyzed in the China Journal of Pharmacology
(1990) the effects of PNS on the synthesis of PGI2 on the arterial
wall and on platelet TXA2 content in mice by using
radioimmunoassay. Results were ig PNS 25, 50, 100 mg/kg for 10 days
continuously. Arterial PGI2 decreased, showing that there may be a
relationship between the inbalance of PGI-TXA2, increased arterial
PGI2 and the anti-AS functions of PNS.
[0543] Hu, Yuejuan (1992) reported in the China Journal of Chinese
Maeteria Medica that coarse extraction of Panax Notoginseng i.p.
can enhance mice's hypoxia tolerance, improve blood circulation and
slow heart rate. It can counteract noradrenaline contraction of the
main artery and relieve the spasms in the smooth muscles of the
intestine. Mice stomach-reperfused with SCC powder suspension
exhibit shortened bleeding and coagulation times. The above
pharmaceutical reactivity of SCC is the same as Panax
Notoginseng.
[0544] Xu, Qing (1993) reported in the China Journal of Chinese
Maeteria Medica on an experiment using Panax Notoginseng leaves
gross saponin 200 mg/kg, 100 mg/kg to perfuse two kinds of high-fat
animals: rats and quail, for 7 days. Cholesterol and triglyceride
levels of the animals were greatly lowered.
[0545] Sun, Jianjun, et al. (1994) reported in the Journal of
Traditional and Herbal Drugs that the condition of patients with
angina pectoris did not improve satisfactorily with traditional
Chinese medicine, which typically removes blood stasis and promotes
blood flow, with nitrate, or with Propranolol, and other medicine.
However, after taking Panax Notoginseng together with those
medications, or Panax Notoginseng alone, 10 out of 11 patients
showed satisfactory progress after a one-month treatment.
[0546] Jiang, Wende (1979) reported in Acta Pharmaceutica Sinica
that using a 0.5 g/tablet of borneol to infuse the stomach of
anesthetized dogs with acute myocardial infarction caused by
blockage of the coronary artery can slow heartbeat and reduce the
difference between the oxygen content in the arteries and the
veins. It can also lengthen hypoxia tolerance time in mice.
[0547] The invention is made up of the following ingredients and is
ready to be used.
33 Radix Salviae Miltorrhizae 48%.about.97% Panax Notoginseng
2%.about.50% Borneol 0.2%.about.3% Radix Salviae Miltorrhizae
63%.about.94% Panax Notoginseng 4%.about.35% Borneol 0.5%.about.2%
Radix Salviae Miltorrhizae 75.2%.about.90% Panax Notoginseng
9%.about.23.5% Borneol 0.5%.about.1.3% Radix Salviae Miltorrhizae
82.87% Panax Notoginseng 16.21% Borneol 0.92%
[0548] The drug is manufactured according to the following method:
Extract the ground Radix Salviae Miltorrhizae and Panax
Notoginseng. Boil in water. Filter it, collect the filtrate, and
concentrate it. Add ethanol to the concentrated filtrate and leave
for settlement. Collect the clear part of the solution for ethanol
recycling. Concentrate the settled portion into a plaster. Mix the
plaster with borneol and other ingredients to form an agent.
[0549] The detailed manufacturing steps are described as
follows:
[0550] 1. Extract the ground Radix Salviae Miltorrhizae and Panax
Notoginseng according to the above ratio. Add water and extract 2-4
times on heat. The temperature should be 60-100.degree. C. Water
volume should be 4-8 times the gross herb material. Filter and
collect the filtrate, which is then concentrated until the
volume-to-weight ratio is 1 L: 0.7-1.3 kg.
[0551] 2. Add 95% ethanol to the concentrated solution until the
concentration of ethanol is 50-85%. Settle it for 4-24 hrs. Filter
the clear part of the solution. collect the filtrate for ethanol
recycling. Concentrate the filtrate into a plaster with a relative
density of 1.15-1.45.
[0552] 3. Mix the plaster and the above borneol and other
ingredients to make the agent.
[0553] The main manufacturing method is to mix all the plaster,
borneol and other ingredients, heat to melt them and transfer them
to the pill maker. The pills are then poured into paraffin oil at a
low temperature. The paraffin oil is removed, and the pills are
made.
[0554] Polyethylene-6000, with a freezing point of
53.about.58.degree. C., is added 2.about.6 times volume of the
plaster and borneol. The temperature is maintained at
60.about.100.degree. C. The temperature of the paraffin oil is
0.about.10.degree. C. (ideally 5.about.10.degree. C.). The pill
weight is 5.about.50 mg/tablet, and the diameter is 1.95.about.4.29
mm.
[0555] This invention uses modern methods and technology to
increase effective content and quality standards, and guarantee the
safety and efficacy of this drug. This drug is a dripping pill and
solid solvent. It is distributed evenly in the substrate in its
molecular form to create an evenly distributed solid. The accuracy
of dosage can be guaranteed. The drug molecules penetrate the
substrate with no space in vacuum. This increases the stability of
the drug.
[0556] After dissolving the drug and the substrate, the drug can be
evenly distributed in the substrate, condenses to form crystals
which are easily dissolved and absorbed, efficiently increases
biological utilization, and reduces side effects. The drug is taken
sublingually, avoiding the processing in the liver and increasing
bioavailability. The effective ingredient is absorbed into the
blood through the mucous membranes of the mouth and expresses its
functions.
[0557] The following is a description of the animal experiments and
clinical research explaining the effects of DSP.
[0558] DSP Animal Experiment Research
[0559] 1. The Effects of Myocardial Ischemia, Myocardial
Infarction, Blood Flow on Related Coronary Arteries, Myocardial
Oxygen Consumption, and Blood Biochemical Standards of Anesthetized
Dogs.
[0560] The effects of DSP on dogs with myocardial ischemia and
myocardial infarction were observed. Based on changes in myocardial
oxygen consumption and biochemical standards, its pharmaceutical
effects on curing coronary heart disease were investigated.
[0561] 1.1 Experimental Groups. (1) Blank control group, normal
saline 3 ml/kg; (2) DSP group, 2 g natural drug/kg; (3) positive
control group, Ditiazem, 5 mg/kg. All the above samples are diluted
with normal saline to the same volume of 3 ml/kg and were given to
the patient through the duodenum.
[0562] 1.2 Experimental Method. The dogs are anesthetized with
pentobarbital sodium. Chests were opened and coronary arterioles
and the central part of the dorsal lower branch separated and tied
to create an acute myocardial ischemia model. ECGs were recorded
and the level of myocardial ischemia (increased section ST, ST) and
area of myocardial ischemia (the total increased decimal places in
section ST) were calculated. The oxygen content in the coronary
artery was recorded. Blood serum creatine kinase (CK), lactate
dehydrogenase (LDH), ET, TXB2 and 6-Keto-PGF1 were measured. The
oxygen content of the aorta and coronary vein, and blood flow
volume in the coronary arteries were measured to calculate
myocardial oxygen consumption. Blood oxygen content in the coronary
vein was measured to calculate myocardial oxygen content
(myocardial oxygen content=(blood oxygen content in arteries-blood
oxygen content in coronary veins) x blood flow volume in coronary
artery/100).
[0563] The hearts were removed 180 mins after treatment and
weighed, cut into slices, and colored with N-BT. The infarction
area of each slice (N-BT-uncolorized area) and non-infarction area
(N-BT colorized area) were measured. The percentage occupied by the
infarction area in the ventricles was calculated and the whole
heart was weighted.
[0564] The significance of the experimental results was tested by
the t-testing method.
[0565] Results
[0566] 1. Effects and area of myocardial ischemia of dogs. When
compared with the control group, DSP can significantly reduce the
scope and area of myocardial ischemia. See Tables 1.1 and 1.2.
[0567] 2. Effects on the scope of myocardial infarction of dogs.
When compared with the control group, DSP can significantly reduce
the area of infarction. See Table 1.3.
[0568] 3. Effects on venous blood oxygen content in dogs with
myocardial ischemia. When compared with the control group, DSP can
increase coronary venous blood oxygen content. See Table 1.4.
[0569] 4. Effects on blood flow standards in dogs with myocardial
ischemia. When compared with the control group, DSP can suppress
the rise of CK and LDH which are caused by myocardial ischemia and
myocardial infarction, release ET and TXB2, and raise
[0570] 6-Keto-PGF content. See Tables 1.5, 1.6, 1.7.
[0571] Conclusions
[0572] DSP can significantly improve myocardial ischemia and
myocardial infarction, raise the blood oxygen level of venous
sinuses, inhibit the release of CK and LDH caused by damage to
cardiac muscles, lower the activity of blood serum CK and LDH,
suppress the activity of blood vessel substances, ET and TXB2, and
raise the 6-Keto-PGF1/TXB2 ratio.
34TABLE 1.1 The effects of different groups of medicines on
different levels of Acute Myocardial hypoxia (.SIGMA.-ST) Changing
in percentage before dosage After dosage (min) Group Dosage/kg
(100%) 15 30 45 60 90 120 180 Normal Saline 3 ml 301.00 .+-. 337.00
.+-. 319.20 .+-. 325.00 .+-. 328.40 .+-. 342.20 .+-. 329.60 .+-.
301.40 .+-. 16.26 26.54 15.22 17.51 15.69 30.69 19.74 25.18 (n = 5)
(100%) 112.27 .+-. 106.37 .+-. 108.19 .+-. 109.39 .+-. 114.04 .+-.
109.76 .+-. 100.47 .+-. 11.18 8.81 7.63 8.35 13.37 8.94 11.54
Ditiazem 5 mg 302.80 .+-. 277.80 .+-. 226.20 .+-. 213.40 .+-.
186.20 .+-. 175.20 .+-. 468.00 .+-. 122.80 .+-. 5.12 31.13 39.71#
40.40# 40.75## 41.11## 47.16## 33.76### (n = 5) (100%) 91.83 .+-.
74.87 .+-. 70.59 .+-. 61.61 .+-. 57.95 .+-. 55.60 .+-. 40.63 .+-.
10.98* 14.10** 13.85*** 14.00*** 13.94*** 16.05*** 11.43*** Dan
Shen Pill 2 g 291.40 .+-. 256.00 .+-. 245.80 .+-. 268.20 .+-.
246.80 .+-. 243.00 .+-. 201.60 .+-. 177.80 .+-. 17.85 50.45 60.34
58.15 69.83 57.51 50.05## 54.22## (n = 5) (100%) 87.95 .+-. 84.06
.+-. 91.57 .+-. 83.97 .+-. 82.78 .+-. 68.90 .+-. 60.56 .+-. 16.89*
18.59* 17.03 20.83* 16.16* 14.48*** 15.91** Notes: Comparison with
control group: *P < 0.05 **P < 0.01 ***P < 0.001
Comparison with the situation before dosage: #P < 0.05 ##P <
0.01 ###P < 0.001
[0573]
35TABLE 1.2 The effects of different groups of medicines on
different levels of Acute Myocardiohypoxia (N-ST) Changing in
Percentage before dosage After dosage (min) Group Dosage/kg (100%)
15 30 45 60 90 120 180 Normal Saline 3 ml 29.60 .+-. 29.60 .+-.
29.60 .+-. 29.60 .+-. 29.60 .+-. 29.60 .+-. 29.60 .+-. 29.60 .+-.
0.55 0.55 0.55 0.55 0.55 0.55 0.55 0.55 (n = 5) (100%) 100.00 .+-.
100.00 .+-. 100.00 .+-. 100.00 .+-. 100.00 .+-. 100.00 .+-. 100.00
.+-. 0.00 0.00 .000 0.00 0.00 0.00 0.00 Ditiazem 5 mg 30.00 .+-.
29.80 .+-. 29.60 .+-. 29.20 .+-. 28.40 .+-. 27.00 .+-. 26.80 .+-.
25.20 .+-. 0.00 0.45 0.55 1.10 1.52 2.00# 1.64# 1.79## (n = 5)
(100%) 99.33 .+-. 98.67 .+-. 97.33 .+-. 94.67 .+-. 90.00 .+-. 89.33
.+-. 84.00 .+-. 1.49 1.83 3.65 5.06* 6.67* 5.48** 5.96** Dan Shen
Pill 2 g 30.00 .+-. 29.20 .+-. 30.00 .+-. 29.80 .+-. 29.20 .+-.
29.00 .+-. 28.40 .+-. 27.80 .+-. 0.00 1.10 0.00 0.45 1.10 1.22
1.14# 0.45## (n = 5) (100%) 97.33 .+-. 100.00 .+-. 99.33 .+-. 97.33
.+-. 96.67 .+-. 94.67 .+-. 92.67 .+-. 3.65 0.00 3.65 3.65 4.08 3.80
1.49 Notes: Comparison with control group: *P < 0.05 **P <
0.01 ***P < 0.001 Comparison with situation after dosage: #P
< 0.05 ##P < 0.01 ###P < 0.001
[0574]
36TABLE 1.3 The effects of different groups of medicines on
different levels of Acute Myocardial hypoxia (N-ST) Area of
Infarction Myocardial Cardiac Area of Location/ Dosage/ area/
Chamber/ Infarction/ Infarction Cardiac Group kg mm2 mm2 mm2
Location/Heart Chamber Normal Saline 3 ml 13494.2 .+-. 1091.4
5228.6 .+-. 646.0 1110.05 .+-. 218.01 8.48 .+-. 0.48 20.66 .+-.
1.99 Ditiazem 5 mg 14096.5 .+-. 3056.4 5377.8 .+-. 411.2 378.98
.+-. 138.41*** 2.52 .+-. 1.35*** 7.22 .+-. 2.87*** Dan Shen Pill 2
g 16186.1 .+-. 261.3 5641.0 .+-. 365.3 407.70 .+-. 131.42*** 2.56
.+-. 0.84*** 7.82 .+-. 1.94*** Notes: Comparison with control
group: *P < 0.05 **P < 0.01 ***P < 0.001
[0575]
37TABLE 1.4 Effects of different groups of medicines on venous
oxygen volume (VO.sub.2 ml %) After Hypoxia Before (value before
Hypoxia dosage Dosage/ (Normal Changing After Dosage (min) Group kg
value) Percentage (100%) 30 60 90 120 180 Normal Saline 3 ml 18.52
.+-. 2.55 17.58 .+-. 1.61 18.36 .+-. 2.79 16.78 .+-. 2.80 16.84
.+-. 3.23 17.28 .+-. 2.24 17.02 .+-. 2.36 (n = 5) 95.89 .+-. 11.18
104.41 .+-. 12.95 95.28 .+-. 11.64 95.50 .+-. 13.59 98.47 .+-.
11.66 96.78 .+-. 9.70 Ditiazem 5 mg 15.44 .+-. 2.42 16.56 .+-. 1.61
16.08 .+-. 1.13 15.84 .+-. 1.43 15.92 .+-. 1.29 15.20 .+-. 1.50
14.82 .+-. 2.28 (n = 5) 111.45 .+-. 33.86 97.70 .+-. 10.36 95.95
.+-. 8.27 96.37 .+-. 5.54 92.15 .+-. 9.42 89.62 .+-. 11.94 Dan Shen
Pill 2 g 16.46 .+-. 3.38 17.46 .+-. 2.69 17.50 .+-. 2.58 16.98 .+-.
1.94 15.80 .+-. 2.01# 15.60 .+-. 2.60# 15.28 .+-. 2.87# (n = 5)
107.17 .+-. 8.78 100.36 .+-. 3.92 97.79 .+-. 5.54 90.83 .+-. 3.67
89.37 .+-. 6.70 87.32 .+-. 7.01 Notes: Comparison with situation
before dosage: #P < 0.05 ##P < 0.01 ###P < 0.001
[0576]
38TABLE 1.5 Comparison of the effects of different medicines on
blood Serum CK (U/L) and LDH (U/L) After Hypoxia before Dosage
Before Changing in Dosage Hypoxia Percentage After dosage (min)
Group ml/kg (Normal) (100%) 30 60 CK Normal 3 ml 310.60 .+-. 56.08
442.40 .+-. 90.32# 533.80 .+-. 89.96# 644.20 .+-. 130.96# Saline (n
= 5) 144.27 .+-. 24.29 123.19 .+-. 20.86 147.64 .+-. 25.98 Ditiazen
5 mg 316.20 .+-. 63.04 699.60 .+-. 211.52# 660.40 .+-. 184.88
737.80 .+-. 159.04 (n = 5) 219.80 .+-. 38.93** 97.20 .+-. 12.50*
108.84 .+-. 20.71* Dan Shen 2 g 399.00 .+-. 25.60 546.40 .+-.
92.88# 746.60 .+-. 286.32 994.00 .+-. 357.60 Pill (n = 5) 136.52
.+-. 21.54 133.85 .+-. 42.37 177.26 .+-. 44.50 LDH Normal 3 ml
120.00 .+-. 46.00 214.60 .+-. 54.08# 214.60 .+-. 54.08# 216.60 .+-.
46.08# Saline (n = 5) 137.36 .+-. 16.71 137.36 .+-. 16.71 140.08
.+-. 21.23 Diltiazen 5 mg 106.40 .+-. 19.12 143.40 .+-. 28.64
143.40 .+-. 28.64 134.40 .+-. 46.48 (n = 5) 101.14 .+-. 17.90*
101.14 .+-. 17.90* 92.58 .+-. 15.17** Dan Shen 2 g 131.80 .+-.
17.04 185.20 .+-. 38.24 185.20 .+-. 38.24 193.80 .+-. 43.76 Pill (n
= 5) 90.81 .+-. 11.17*** 90.81 .+-. 11.17*** 95.19 .+-. 10.21**
After dosage (min) Group 90 120 180 CK Normal 857.60 .+-. 262.32#
960.80 .+-. 247.68# 1157.60 .+-. 180.72## Saline (n = 5) 191.80
.+-. 26.52 219.41 .+-. 45.62 268.67 .+-. 35.47 Ditiazen 820.80 .+-.
289.76 972.40 .+-. 347.28 1238.60 .+-. 309.12## (n = 5) 115.31 .+-.
19.97*** 314.91 .+-. 23.35** 179.51 .+-. 10.60*** Dan Shen 944.20
.+-. 250.16# 1097.80 .+-. 268.48# 1097.40 .+-. 235.84# Pill (n = 5)
172.86 .+-. 40.89 197.71 .+-. 34.95 200.03 .+-. 29.77* LDH Normal
221.00 .+-. 64.00# 221.80 .+-. 39.36## 252.80 .+-. 72.96# Saline (n
= 5) 140.51 .+-. 13.77 145.73 .+-. 15.56 162.51 .+-. 16.19
Diltiazen 153.00 .+-. 70.80 194.60 .+-. 76.72 164.80 .+-. 49.36 (n
= 5) 93.31 .+-. 19.02** 121.32 .+-. 22.12 117.24 .+-. 26.69* Dan
Shen 175.00 .+-. 31.20 195.20 .+-. 41.04 191.80 .+-. 28.69* Pill (n
= 5) 87.87 .+-. 15.53*** 98.96 .+-. 18.62** 191.80 .+-. 28.96
Notes: Comparison with control group: *P< 0.05 **P < 0.01
***P < 0.001 Comparison with situation before dosage: #P <
0.05 ##P < 0.01 ###P < 0.001
[0577]
39TABLE 1.6 Comparison of the effects of different medicines on
blood plasma ET (pg/ml) and TXB.sub.2 (pg/ml) After Hypoxia before
dosage) and Changing Before in Dosage/ Hypoxia percentage After
Dosage (min) Group kg (Norma) (100%) 30 60 ET Normal 3 ml 39.47
.+-. 12.59 47.59 .+-. 5.79 61.38 .+-. 10.66## 60.70 .+-. 12.19 (n =
5) 131.40 .+-. 33.06 128.97 .+-. 13.55 127.94 .+-. 20.07 Diltiazem
5 mg 34.41 .+-. 9.41 55.51 .+-. 3.59 47.51 .+-. 7.39 46.38 .+-.
9.02 (n = 5) 178.30 .+-. 57.33 85.14 .+-. 13.98** 84.06 .+-.
18.24** Dan Shen 2 g 50.98 .+-. 2.53 74.98 .+-. 10.42 65.03 .+-.
14.86 76.38 .+-. 12.16 Pill (n = 5) 146.82 .+-. 18.13 87.34 .+-.
16.19** 102.16 .+-. 10.76* TXB2 Normal 3 ml 120.00 .+-. 46.00
214.60 .+-. 54.08# 214.60 .+-. 54.08# 216.60 .+-. 46.08# Saline (n
= 5) 137.36 .+-. 16.71 137.36 .+-. 16.71 140.08 .+-. 21.23
Diltiazem 5 mg 106.40 .+-. 19.12 143.40 .+-. 28.64 143.40 .+-.
28.64 134.40 .+-. 46.48 (n = 5) 101.14 .+-. 19.90* 101.14 .+-.
17.90* 92.58 .+-. 15.17** Dan Shen 2 g 131.80 .+-. 17.04 185.20
.+-. 38.24 185.20 .+-. 38.24 193.80 .+-. 43.76 Pill (n = 5) 90.81
.+-. 11.17*** 90.81 .+-. 11.17*** 95.19 .+-. 10.21** After Dosage
(min) Group 90 120 180 ET Normal 55.40 .+-. 10.73 60.83 .+-. 6.64#
67.38 .+-. 6.37## (n = 5) 122.34 .+-. 38.90 130.39 .+-. 21.06
143.28 .+-. 12.27 Diltiazem 39.97 .+-. 7.95# 41.42 .+-. 15.69 45.74
.+-. 9.40 (n = 5) 71.69 .+-. 12.10* 74.30 .+-. 17.04** 82.16 .+-.
14.09*** Dan Shen 55.96 .+-. 5.19# 69.90 .+-. 17.26 69.39 .+-.
26.20 Pill (n = 5) 75.64 .+-. 6.72* 93.30 .+-. 20.94 90.15 .+-.
34.40* TXB2 Normal 1511.9 .+-. 252.2 1164.9 .+-. 223.0 1268.1 .+-.
154.8 Saline (n = 5) 114.06 .+-. 8.07 116.22 .+-. 8.09 134.90 .+-.
31.09 Diltiazem 1093.4 .+-. 320.9 1284.1 .+-. 695.0 1032.7 .+-.
343.1 (n = 5) 69.72 .+-. 8.76*** 63.03 .+-. 14.20*** 62.77 .+-.
14.51* Dan Shen 938.7 .+-. 46.4 883.6 .+-. 107.7## 902.6 .+-.
118.3# Pill (n = 5) 90.11 .+-. 14.32 83.00 .+-. 3.65*** 84.67 .+-.
5.80** Notes: Comparsion with control group: *P < 0.05 **P <
0.01 ***P < 0.001 Comparison with situation before dosage: #P
< 0.05 ##P < 0.01 ###P < 0.001
[0578]
40TABLE 1.7 Comparison of the effects of different medicines on
6-Keto-PGF.sub.1.alpha. and 6-Keto-PGF.sub.1.alpha./TXB.sub.- 2
After Hypoxia before dosage and Before Changing hypoxia in Dosage/
(Normal percentage After dosage (min) Group kg value (100%) 30 60
6-Keto- PGF.sub.1.alpha. Normal 3 ml 1673.2 .+-. 221.0 1469.0 .+-.
283.6# 1200.6 .+-. 335.3# 1099.2 .+-. 301.0### Saline (n = 5) 87.15
.+-. 7.49 80.77 .+-. 10.26 73.79 .+-. 6.64 Diltiazem 5 mg 1597.4
.+-. 185.3 1478.8 .+-. 218.6 1749.4 .+-. 278.3 1902.6 .+-. 155.1#
(n = 5) 92.3 .+-. 5.53 118.95 .+-. 14.47** 131.19 .+-. 16.98*** Dan
Shen 2 g 1763.0 .+-. 361.6 1417.4 .+-. 365.5# 1471.6 .+-. 365.5#
1649.4 .+-. 280.7 Pill (n = 5) 80.76 .+-. 6.68 100.50 .+-. 20.80
132.71 .+-. 51.64* 6-Keto- PGF.sub.1.alpha./ TXB.sub.2 Normal 3 ml
120.00 .+-. 46.00 214.60 .+-. 54.08# 1.174 .+-. 0.383# 1.037 .+-.
0.381# Saline (n = 5) 137.36 .+-. 16.71 73.30 .+-. 4.14 65.57 .+-.
8.52 Diltiazen 5 mg 106.40 .+-. 19.12 143.40 .+-. 28.64 1.507 .+-.
0.505## 1.501 .+-. 0.358# (n = 5) 101.14 .+-. 17.90* 148.42 .+-.
17.35*** 155.44 .+-. 28.97*** Dan Shen 2 g 131.80 .+-. 17.04 185.20
.+-. 38.24 1.523 .+-. 0.441 1.764 .+-. 0.270 Pill (n = 5) 90.81
.+-. 11.17*** 108.02 .+-. 21.11** 158.76 .+-. 77.62* After dosage
(min) Group 90 120 180 6-Keto- PGF.sub.1.alpha. Normal 1056.2 .+-.
210.2## 1095.0 .+-. 215.2# 1052.8 .+-. 187.7## Saline (n = 5) 72.39
.+-. 5.92 75.39 .+-. 8.57 72.29 .+-. 7.21 Diltiazem 1912.4 .+-.
258.5 1982.8 .+-. 574.2 1705.2 .+-. 412.2 (n = 5) 132.75 .+-.
28.52** 139.39 .+-. 56.36* 119.08 .+-. 39.78 Dan Shen 1557.2 .+-.
251.0 1138.2 .+-. 124.6 1202.6 .+-. 270.3 Pill (n = 5) 129.31 .+-.
61.64 88.35 .+-. 25.15 90.26 .+-. 21.03 6-Keto- PGF.sub.1.alpha./
TXB.sub.2 Normal 1.037 .+-. 0.381# 1.040 .+-. 0.368# 0.852 .+-.
0.218 Saline (n = 5) 65.67 .+-. 11.87 65.67 .+-. 11.87 57.95 .+-.
11.77 Diltiazen 1.980 .+-. 0.924 1.980 .+-. 0.924 1.801 .+-. 0.596
(n = 5) 203.82 .+-. 83.25** 203.82 .+-. 83.25** 198.48 .+-. 87.02**
Dan Shen 1.320 .+-. 0.254 1.320 .+-. 0.254 1.388 .+-. 0.388 Pill (n
= 5) 105.35 .+-. 25.55* 105.35 .+-. 25.55* 105.05 .+-. 19.85**
Notes: Comparison with control group: *P < 0.05 **P < 0.01
***P < 0.001 Comparison with situation before dosage: #P <
0.05 ##P < 0.01 ###P < 0.001
[0579] 2. The Protection of Myocardial Ischemical Reperfusion
Injury from Hypoxia in Rats
[0580] This research stresses the effects of Dan Shen Pill in
myocardial ischemical reperfusion injury from hypoxia in rats,
especially on the apoptosis of myocardial cells.
[0581] 1. Animal Models. Wistars are male rats. They were given
anesthesia, and their chests were opened while they continued
breathing. The coronary artery was tied at the conical area between
the left atrium and the pulmonary artery.
[0582] 2. Methods. The rats were assigned to 5 random groups: a)
Sham-operated control. Perfuse the normal saline to the stomach, 1
ml/day, 4 days in total. b) Myocardial ischemia reperfusion (M-IR).
The same reperfusion method as above. c) Dissolve the compound Dan
Shen Pill I (DSPI) 150 ml/kg/day in 1 ml of normal saline. Infuse
the stomach (the same method as above). d) Dan Shen Pill II
(DSPII), 300 ml/kg/day. The other specifications are the same as
those used with DSP I. e) Dan Shen Pill (DSPIII), 450 ml/kg/day.
The other specifications are the same as those used with DSPI.
[0583] Testing Standard:
[0584] 2.1 Testing of myocardial infarction area. The left coronary
artery was retied before the rat died. The auricles were removed
after priming with 1% of Evan's Blue and bleached with PBS. They
were kept in ice for 1 h. After removing the unnecessary cells,
they were colored in 1% TTC for 30 min (37.degree. C.). The
myocardial hypoxia emergency area (Uncolored Evan's blue Area) and
infarction area (Uncolored TTC Area) were calculated by
weighing.
[0585] 2.2 Testing and analysis of in-situ labeling of myocardial
apoptotic cells. 3 slices of flesh were taken from 3 different
parts of each of the hearts. The 3'-OH end of DNA in the nuclei of
the myocardial apoptotic cells was labeled with nicked-end TdT
isomerase by TdT-mediate flourescein-duTP nick-end labeling, TUNEL.
5 different views were chosen. 300 positive cells inside the
myocardial cells in each view were counted. The average positive
cell count percentage was used as the apoptotic index, AI.
[0586] Results
[0587] Change in myocardial infarction area. Myocardial infarction
did not occur after 7 hrs of sham operation. Myocardial hypoxia
occurred for 1 hr and myocardial infarction occurred sharply after
reperfusing for 6 hrs. DSP can reduce the M-IR area and increase
the effects with increasing dosage. Myocardial infarction area was
minimized as shown in the following Table 2.1.
41TABLE 2.1 Changes of myocardial infarction area in different
groups Infarction Area weight/ Infarction Area weight/ Group left
ventricle weight (%) risty Area weight (%) Sham-control 0 0 M-IR
41.8 .+-. 7.9 63.2 .+-. 8.6 DSPI 34.6 .+-. 7.2**.sup..quadrature.
55.7 .+-. 8.4* DSPII 27.1 .+-. 6.5**.sup..quadrature. 47.3 .+-.
7.7**.sup..quadrature. DSPIII 19.4 .+-.
6.1**.sup..quadrature..quadrature..quadrature. 38.9 .+-.
7.5**.sup..quadrature..quadrature..quadrature. Notes: Comparison
with M-IR group, *P < 0.05, **P < 0.01; Comparison with DSP I
group, .sup..DELTA.P < 0.05, .sup..DELTA..DELTA.P < 0.01;
Comparison with DSPII group, .sup..diamond.P < 0.05.
[0588] 3.2 Change in myocardial apoptotic cells. Comparatively
large amounts of DSP can sharply reduce the number of M-IR
apoptotic cells, and AI drops with increasing dosage of DSP, as
shown in Table 2.2.
42TABLE 22 Change in number of different groups of myocardial
apoptotic cells Group Case number Myocardial cells AI (%) Sham- 10
0.82 .+-. 0.47 control M-IR 10 22.76 .+-. 13.17 DSPI 10 20.93 .+-.
13.25* DSPII 10 16.28 .+-. 11.96*.sup..DELTA..diamond. DSPIII 10
10.75 .+-. 9.44.sup..DELTA..DELTA..diamond..tangle-solidup. Notes:
Comparison with Sham-control group, *P < 0.01; Comparison with
M-IR group, .sup..quadrature.P < 0.05,
.sup..quadrature..quadrature.P < 0.01; Comparison with DSPI
group, P < 0.05, .sup..diamond..diamond.P < 0.01; Comparison
with DSPII group, .sup..tangle-solidup.P < 0.05
[0589] Conclusion
[0590] This research proves that DSP could sharply minimize the
myocardial infarction area in the M-IR group of rats. This further
shows that DSP can do a good job of protecting the myocardial cells
of the M-IR group.
[0591] 3. Propagation of Myocardial Hypoxia in Mice and Effects of
Fas/FasL Proteins under Deoxygenation and
Deoxygenation/Re-Oxygenation Conditions.
[0592] Fas gene is an apoptosis-stimulating gene. Its expressed
protein product, Fas antigen, is a cell membrane protein. Recently,
it was discovered, in experiments on propagation of myocardial
hypoxia, that there is a close relationship between the expressed
mRNA of Fas gene and myocardial apoptosis. FasL is the ligand of
Fas. It is on the surface of transmembrane proteins, which is
homologous to the TNF. It can bind to the receptor Fas on the
surface of the cell and give out the death signal.
[0593] 1. Method. The myocardial cells of newborn mice were
propagated normally. Hypoxia and deoxygenation/re-oxygenation
testing was carried out after 24 hrs of propagation. The change in
Fas/FasL protein expression level was then tested by the secondary
immune system.
[0594] 2. Results 1. Change in Fas/FasL protein expression in the
group with hypoxia for 4.5 hrs, group with hypoxia for 30 mins, and
group with re-oxygenation for 4 hrs. The Fas/FasL protein
expressions of both groups increased sharply compared with the
control one. Protein expression of the Fas/FasL of DSP-protected
group dropped more dramatically than the unprotected one, as shown
in Table 3.1.
[0595] 2. Change in Fas/FasL protein expression in the group with
hypoxia for 10.5 hrs, group with hypoxia for 30 mins, and group
with re-oxygenation for 10 hrs. The Fas/FasL protein expressions of
both groups increased sharply compared with the control. The
protein expression of the Fas/FasL of the DSP-protected group
dropped more dramatically than the unprotected one, as shown in
Table 3.2.
[0596] 3. There is more likelyan increasing trend to the Fas/FasL
protein expression in the group with hypoxia for 10. 5 hrs than in
the group with hypoxia for 4.5 hrs, but there is no major
difference between them.
[0597] 4. There was no major difference between the group with
re-oxygenation for 10.5 hrs and the group with re-oxygenation for
4.5 hours.
[0598] 5. There was a correlation in the protein expression of
Fas/FasL.
[0599] The above results show DSP can reduce apoptosis by
interfering with Fas/FasL expression, protecting the cells from
damage by hypoxia and deoxygenation/re-oxygenation.
43TABLE 3.1 The change in Fas/FasL protein expression in group with
hypoxia for 4.5 h, group with hypoxia for 30 mins, re-oxygenation
for 4 hrs. Fas protein PEI (%) FasL protein PEI (%) DSP DSP
unprotected protected unprotected protected Control 2.59 2.61 2.27
2.26 group Group with 18.01* 9.62** 19.67* 10.74** hypoxia for 4.5
hrs Group with 19.02* 10.00** 20.71* 10.69** Re- oxygenation for 4
hrs Notes: Comparison with control group, *P < 0.05 Comparison
with DSP unprotected group, **P < 0.05
[0600]
44TABLE 3.2 The change of Fas/FasL protein expression in the group
with hypoxia for 10.5 hrs, group with hypoxia for 30 mins,
re-oxygenation for 1O hrs. Fas Protein PEI (%) FasL Protein PEI (%)
DSP DSP unprotected protected unprotected protected Control 2.89
2.22 2.22 2.11 group Group with 21.75* 11.64** 22.83* 14.20**
hypoxia for 10.5 hrs Group with 19.70* 12.95** 22.12* 13.08**
re-oxygenation for 10 hrs Notes: Comparison with control group *P
< 0.05, Comparison with DSP unprotected group **P < 0.05
[0601] 4. Effects on Lipidemia and Atherosclerosis in Rabbits
[0602] 1. Method
[0603] 1.1 Experimental Groups. (1) Normal control group (8
rabbits) normal feeding; (2) High-fats group: High-fats feeding.
All were fed for 4 weeks. Weight and lipoprotein in the blood were
measured. The high-fats group was divided into 4 sub-groups (12
rabbits in each sub-group). 1. High-fats control group, 2.
High-dosage of DSP group (4 g dosage/kg/day), 3. Low-dosage DSP
group (2 g dosage/kg/day), and 4. Simvastatin group (1 mg/kg/day).
All are given distilled water except those with special
prescriptions and ends after 12 weeks testing.
[0604] 1.2 Experimental Methods and Standards. (1) Examination of
Aortic Lesion. Drugs were given to the animals for 8 weeks, and
then the animals were killed. The aortas were removed and the
unnecessary membranes and fats discarded. The aortas were cut open
along the mid line. One-fifth of the aorta was removed for lipid
examination. The remaining part was colored by Sudan III and used
to calculate the spotting plate area and the total area of the
aorta. The percentage of the lesion part was calculated, and a
grading was given. The aorta was positionally cut to make paraffin
slices. It was colored by HE. The average thickness of the interior
membrane spot plates was measured by microscopic parameter. (2)
Examination of coronary artery lesion. The lower 0.4 cm of the
coronary artery colpus and 0.8 cm of the apex cordis were
transected to make 3 small plates. Sudan III colorization was
carried out. The number of blood vessels with spot plates in the
coronary artery and the lesion percentage (lesion percentage =the
number of blood vessels with lesion/the total number of blood
vessels in each transect X100%) were observed, calculated and
graded according to the blocking of the blood vessels with spot
plates. The average points were calculated by accumulation.
[0605] Results
[0606] (1) Effects on lipoprotein in blood serum of rabbits. The
testing showed that the markings are lower than that of the
high-fats group 2, 4, 8 weeks after taking DSP, as shown in Table
4.1.
[0607] (2) Aorta AS area. It was observed that the interior
membrane of the aorta was smooth and shiny without AS spot plates
or streaks. The aortic lesion area percentage of the group with DSP
protection was obviously smaller than that of the high-fats group
(P<0.05). Lipoprotein level in aorta. Drugs were given for 8
weeks. The aortic TC and TG in the high-fats control group were
obviously higher than that in the normal control group
(P<0.001). TC in the DSP-protected group was obviously higher
than that in the high-fats control group, as shown in Table
4.2.
[0608] (3) Effects on liver coefficient and lipoprotein level in
the liver. The testing showed that the DSP-protected group and
high-fats control group ratio can lower TG content (P<0.05), as
shown in Table 4.3.
[0609] Conclusion
[0610] The testing showed that DSP can lower TC, TG, LDL-C, VLDL-C
concentration, and TC/HDL-C ratio in the blood serum in rabbits.
DSP also reduced the thickness of the aortic spot plate and the
area of the aortic spot plates. DSP could adjust lipoprotein level
and prevent atherosclerosis to a certain extent.
45TABLE 4.1 Effects on the lipoprotein content in blood serum of
rabbits (mmol/L, n = 8, x .+-. s) Time Group Dosage TC LDC-C VLDC-C
TC/HDL-C TG B/f Normal 2.23 .+-. 0.19 0.79 .+-. 0.20 0.41 .+-. 0.20
2.25 .+-. 0.59 0.74 .+-. 0.17 testing control Highfat 2.31 .+-.
0.22 0.94 .+-. 0.16 0.42 .+-. 0.24 2.58 .+-. 0.80 0.74 .+-. 0.21
control DSP 4 g 2.26 .+-. 0.14 0.91 .+-. 0.14 0.50 .+-. 0.19 2.75
.+-. 0.59 0.81 .+-. 0.18 DSP 2 g 2.21 .+-. 0.19 0.84 .+-. 0.17 0.40
.+-. 0.12 2.30 .+-. 0.29 0.78 .+-. 0.30 Simvastatin 1 mg 2.27 .+-.
0.18 0.87 .+-. 0.21 0.51 .+-. 0.27 2.72 .+-. 0.85 0.72 .+-. 0.15
A/fter Normal 2.19 .+-. 0.20*** 0.87 .+-. 0.20*** 0.45 .+-. 0.12***
2.51 .+-. 0.30*** 0.83 .+-. 0.21** dosage Control Highfat 26.69
.+-. 3.86 19.40 .+-. 4.19 6.42 .+-. 2.31 31.17 .+-. 9.49 2.25 .+-.
1.03 control DSP 4 g 27.48 .+-. 6.83 20.25 .+-. 6.80 6.34 .+-. 2.57
32.07 .+-. 9.70 2.10 .+-. 0.74 DSP 2 g 28.43 .+-. 5.46 20.77 .+-.
6.55 6.84 .+-. 2.28 36.51 .+-. 12.31 2.25 .+-. 0.86 Simvastatin 1
mg 26.92 .+-. 7.72 19.69 .+-. 8.33 6.35 .+-. 1.42 31.68 .+-. 10.14
2.04 .+-. 1.00 2 weeks Normal 2.15 .+-. 0.34*** 0.88 .+-. 0.22***
0.37 .+-. 0.14*** 2.43 .+-. 0.42*** 0.74 .+-. 0.10*** after control
dosage Highfat 34.15 .+-. 6.97 26.66 .+-. 6.21 6.65 .+-. 1.40 43.02
.+-. 11.38 3.01 .+-. 0.84 Control DSP 4 g 24.81 .+-. 6.94* 16.54
.+-. 6.99** 7.39 .+-. 1.93 29.62 .+-. 11.16* 1.60 .+-. 0.56** DSP 2
g 31.74 .+-. 7.91 25.27 .+-. 7.45 5.66 .+-. 1.70 39.31 .+-. 7.23
2.12 .+-. 0.91 Simvastatin 1 mg 27.06 .+-. 4.46* 19.54 .+-. 5.71*
6.66 .+-. 1.65 32.29 .+-. 7.39* 1.85 .+-. 0.55** 4 weeks Normal
2.30 .+-. 0.20*** 0.97 .+-. 0.30*** 0.38 .+-. 0.19*** 2.48 .+-.
0.41*** 0.78 .+-. 0.17*** after Control dosage Highfat 37.87 .+-.
6.92 27.73 .+-. 7.19 9.06 .+-. 2.30 35.95 .+-. 9.19 2.84 .+-. 0.71
control DSP 4 g 25.96 .+-. 5.64** 18.06 .+-. 6.02* 6.72 .+-. 1.46*
22.19 .+-. 5.07** 1.74 .+-. 0.39** DSP 2 g 35.46 .+-. 8.86 27.41
.+-. 8.17 6.94 .+-. 1.17* 32.56 .+-. 8.52 2.34 .+-. 0.33
Simvastatin 1 mg 26.1 .+-. 3.03*** 18.22 .+-. 3.37** 6.54 .+-.
0.74* 19.6 .+-. 4.38*** 1.80 .+-. 0.31** 8 weeks Normal 2.06 .+-.
0.26*** 0.64 .+-. 0.44*** .044 .+-. 0.28*** 2.14 .+-. 0.41*** 0.80
.+-. 0.27*** after Control dosage High Fat 46.19 .+-. 8.26 32.04
.+-. 9.69 13.37 .+-. 3.51 64.27 .+-. 21.3 4.34 .+-. 1.45 Control
DSP 4 g 27.8 .+-. 7.99*** 19.35 .+-. 8.05* 7.44 .+-. 2.17** 26.9
.+-. 10.76** 2.73 .+-. 0.75* DSP 2 g 32.47 .+-. 4.73** 22.59 .+-.
4.94* 8.91 .+-. 2.17** 35.8 .+-. 11.72** 3.67 .+-. 0.88 Simvastatin
1 mg 26.3 .+-. 4.40*** 17.78 .+-. 5.69** 7.30 .+-. 2.05*** 22.3
.+-. 6.54*** 2.70 .+-. 0.77* Notes: Comparison with high-fats
control group *P < 0.05, **P < 0.01, ***P < 0.001
[0611]
46TABLE 4.2 Effects on lipoprotein content in aorta Dosage Group
(/kg/Day) Number of animal (n) TC Normal 8 0.51 .+-. 0.08***
Control High-fats 8 7.80 .+-. 2.07 Control DSP 4 g.sup. 8 5.30 .+-.
1.62* DSP 2 g.sup. 8 5.51 .+-. 1.86* Simvastatin 1 mg 8 4.93 .+-.
2.62* Notes: Comparison with high-fats control group *P < 0.05,
***P < 0.001
[0612]
47TABLE 4.3 Effects on hepatocytic tissue TG and liver coefficient
Dosage TG Liver Coefficient Group (/kg) (mg/tissue organ) (g/100 g
weight Normal Control 5.50 .+-. 1.05* 2.83 .+-. 0.36*** High-fats
9.70 .+-. 1.69 5.57 .+-. 0.78 Control DSP 4 g 7.38 .+-. 1.67* 5.08
.+-. 0.77 DSP 2 g 8.76 .+-. 0.86 5.80 .+-. 1.16 Simvastatin 1 mg
7.44 .+-. 1.49* 5.16 .+-. 0.60 Notes: Comparison with high-fats
control group *P < 0.05, ***P < 0.001
[0613] 5. Anti-Oxidation and Removal of Free Radicals
[0614] Effects on MDA and SOA in the blood serum on M-IR damage By
comparing the effect of Diltiazem and the effects of DSP on M-IR
and its correlated biochemical markers, MDA and SOD can be
observed.
[0615] 1. Method:
[0616] (1) Experimental Groups. Control group (Serum taken as
normal control), Model group (Normal Saline), Ditiazem group (30
mg/kg), DSP 6.0,3.0 g/kg group. Each group was diluted to its
necessary concentration with 3 ml/kg normal saline through the
duodenum.
[0617] (2) Experimental Method. Wistar animal is anesthetized by
pentobarbital sodium and fixed. Chests and cardial membranes are
opened to expose the heart. A hole in the left lower dorsal part of
the coronary artery is left for tying. Separate the duodenum, and
infuse the tested drugs into it. Take blood from the abdomen after
2 hrs and test the MDA and SOD content in the blood serum.
[0618] Results
[0619] The SOD activity of DSP group increased. There was an
obvious difference when compared with the control group
(P<0.01), but the effects on MDA could not yet be observed, as
shown in Table 5.1.
48TABLE 5.1 Effects of DSP on SOD activity and MDA content in blood
serum Group Dosage SOD (U/ml) MDA (.mu. mol/L) .times. 10.sup.-3
Normal control 830.8 .+-. 31.9 2.60 .+-. 0.35 Model 627.7 .+-.
70.9## 5.42 .+-. 0.97## Ditiazem 30 mg 817.6 .+-. 115.6** 5.29 .+-.
1.07 DSP 3.0 g/kg 801.7 .+-. 74.6** 5.83 .+-. 1.24 6.0 g/kg 794.2
.+-. 122.6** 5.43 .+-. 1.06 Notes: ##Comparison with normal control
group, P < 0.01; **Comparison with model group, P < 0.01.
[0620] Conclusion
[0621] DSP provides protection from injuries caused by reperfuion
of ischemic area and increases the activity of SOD.
[0622] Effects on SOD activity and MDA content in rabbit blood
serum and liver
[0623] Method. The experimental groups were divided into: (1)
Normal control group. Normal feeding; (2) High-fats feeding group:
high-fats feeding.
[0624] All were fed for 4 weeks. weight and lipoprotein content in
the blood were measured. The high-fats feeding group was divided
into 4 sub-groups: a) High-fats control group, b) High-dosage DSP
group (4 g raw medicine/kg/day), c) Low-dosage DSP group (2 g raw
medicine/kg/day), d) Simvastatin group (1 mg/kg/day). Medicine was
given to the rabbits through the stomach, according to
prescription. The same volume of distilled water was given to the
normal control group and high-fats feeding group. Testing ended
after 12 weeks.
[0625] Results
[0626] (1) Measurement of blood serum MDA and SOD showed that the
MDA content of the high-fats feeding group was much higher than
that of the normal control group after 8 weeks of treatment
(P<0.01). However, there is no significant SOD activity
difference compared with that of the normal control group. No
significant differences can be found in SOD activity and MDA
content between the high-fats control group and each of the
medicated-given groups.
[0627] (2) Measurement of MDA and SOD in liver shows that the MDA
content of the high-fats feeding group is much higher than that of
the normal control group after 8 weeks of treatment (P<0.001).
SOD activity was much lower than that of the normal control group
(P<0.001). The liver MDA contents of both the high-dosage DSP
group and the Simvastatin group were much lower than that of the
high-fats control group (P<0.001). SOD activity of each of the
medicated groups was much higher than that of the high-fats control
group (P<0.01), as shown in Table 5.2.
49TABLE 5.2 Effects of DSP on SOD activity and MDA content on
rabbit liver (x .+-. s) Blood serum Liver SOD MDA (10.sup.3 u/g
(10.sup.3 u/g Dosage SOD MDA tissue tissue Group (/kg/d) n (u/ml)
(nmol/ml) weight) weight) Normal 8 776.9 .+-. 72.8 2.73 .+-. 0.42**
12.85 .+-. 0.50*** 189.1 .+-. 30.0** Control High-fats 8 754.7 .+-.
44.2 6.82 .+-. 3.54 9.87 .+-. 0.98 387.3 .+-. 38.3 control DSP 4 g
raw 8 781.7 .+-. 152.3 6.24 .+-. 3.22 11.67** .+-. 0.82 256.3 .+-.
20.0*** medicine 2 g raw 8 772.4 .+-. 84.8 6.24 .+-. 2.16 11.37
.+-. 0.59** 325.7 .+-. 119.9 medicine Simvastatin 1 mg 8 816.7 .+-.
77.2 5.63 .+-. 1.30 11.62 .+-. 0.38*** 249.3 .+-. 42.6*** Notes:
Comparison with high-fats control group, **P < 0.01 ***P <
0.001
[0628] MDA is the main catabolic product of the oxidation of fats.
It can damage the structure of the cell membrane so seriously that
heart and liver tissues are damaged. SOD has an effective action of
clearance on superoxide anions. It can regulate the oxidation
reaction controlled by free radicals. DSP can increase SOD
activity, decrease MDA content, lower the oxidation standard, and
reduce the level of damage to the organs.
[0629] 6. Effects on Cardiac Arrhythmia Caused by Exogenous Free
Radicals
[0630] Langendorff perfusion device was used to pour ferrous
sulfate (0.25 mmol/L)/citrate (1.0 mmol/L) into the Wistar rat's
artificial heart. The model of free radicals causing heart rhythm
irregularity was replicated to observe the effects of DSP.
[0631] 1. Experimental Groups
[0632] (1) Blank group (Normal control). Reperfused with perfusion
solution for 45 mins continuously. The change in
electrocardiographic pattern was observed.
[0633] (2) SP group. DSP was added in 50 mg/L of perfusion solution
and perfused for 45 mins continuously. The change in
electrocardiographic pattern was observed.
[0634] (3) Free-radical-damaging group (Free radicals). After
pre-perfusing the artificial heart for 15 mins, it was reperfused
with perfusion solution containing ferrous sulfate (0.25
mmol/L)/citrate(1.0 mmol/L) for 30 mins continuously. The change in
electrocardiographic pattern was observed.
[0635] (4) DSP-protected group (DSP+free radicals): DSP was added
into 50 mg/L of perfusion solution and pre-perfused for 15 mins.
Ferrous sulfate (0.25 mmol/L/citrate(1.0 mmol/L) was added to the
perfusion solution and then infuse for 30 mins continuously. The
change in electrocardiographic pattern was observed.
[0636] (5) Verapamil-protected group (verapamil+free radicals). 1
ml/L of verapamil was added to the perfusion solution and
preperfused for 15 mins. Ferrous sulfate (0.25 mmol/L)/citrate (1.0
mmol/L) was added to the priming solution and perfused for 30 mins
continuously. The change in electrocardiographic pattern was
observed.
[0637] Results
[0638] Exogenous free radicals can increase cardiac arrhythmia up
to 100% and atrial cellular lysis up to 43%. 1 mg/L verapamil and
50 mg/L DSP can lower the irregularity percentage to 71.4% and
87.5%, as shown in Table 6.1. It shows that DSP can prevent cardiac
arrhythmia caused by free radicals.
50TABLE 6.1 Effects of DSP on cardiac arrhythmia caused by
exogenous free radicals Atrioven- Total tricular Ventricular
Ventricular Ventria- cardiac dissociation extrasystole overspeed
fibrillation arrhythmia Case Case Case Case Case Case Group number
number % number % number % number % number % Normal 7 0 0 0 0 0 0 0
0 0 0 Control DSP 7 0 0 0 0 0 0 0 0 0 0 Free 7 5 71.4 5 71.4 3 42.7
3 42.7 7 100 radicals Verapamil + Free 6 0 0 1 16.6 1 16.6 0 0 2*
33.3 radicals DSP + Free 8 1 12.5 0 0 0 0 0 0 1** 12.5 radicals
Notes: Comparison with free-radical group, *P < 0.05 **P <
0.001
[0639] 7. Clinical Applications for Acute Pancreatitis in Rats
[0640] This experiment uses the acute pancreatitis model with
multi-organ malfunction in rats to show the change in the blood
plasma endothelins and the clinical applications of DSP.
[0641] 1. Experimental Groups
[0642] Classical reverse bile duct vaccination was used to create
the acute pancreatitis model. The animal used was a Wistar Rat.
[0643] (1) Normal control group (Control group): The bile duct was
not tied. The abdomen was cut open and immediately closed after the
pancreas was removed. Normal saline (5 ml/kg) was injected
subcutaneously 30 mins before the operation and 2 hrs after
operation. Animals were killed 12 hrs after operation.
[0644] (2) Saline treatment group (Saline group): Normal saline (5
ml/kg) was injected subsutaneously 30 mins before the model was
created and 2 hrs after creation. Animals were killed 12 hrs after
the model was created.
[0645] (3) DSP treatment group (DSP group): DSP (400 mg/kg) was
reperfused into the stomach 30 mins before the model was created
and 2 hrs after creation. Animals were killed 12 hrs after the
model was created.
[0646] 2. Results
[0647] Glutamate Phosphate Transferase (GPT), Bilirubin Urea
Nitrate (BUN) and Amylase (Amg) content in the blood serum of the
saline group increased significantly (compared with the normal
control group, P<0.01). GPT, BUN, and Amg content in the DSP
group increased (compared with the normal control group,
P<0.01), but was still lower than that of the saline group
(compared with saline group, P<0.01), as shown in Table 7.1. The
endothelins (ET) content of the saline group increased
significantly (Compared with normal control group, P<0.001). The
ET content of DSP group was much lower than that of the saline
group (P<0.05) and the normal control group P>0.05, as shown
in Table 7.2. Microscopic observation of the change in shape of
pancreatic, liver and lung tissue showed that there was much more
improvement in the DSP group than in the saline group.
51TABLE 7.1 The change in GPT (u/l), BUN (mmol/L), Amg (u) content
in each group Control group Saline group DSP group GPT 48.89 .+-.
10.84 1162.48 .+-. 258.90** 612.13 .+-. 155.50**## BUN 9.04 .+-.
1.47 27.43 .+-. 2.61* 19.74 .+-. 3.23*# Amg 4880 .+-. 1850.07
11970.7 .+-. 1530.65* 9458.4 .+-. 782.32*# Notes: Comparison with
control group, *p < 0.01 **p < 0.001 Comparison with saline
group, #P < 0.01 ##P < 0.001
[0648]
52TABLE 7.2 Change in blood plasma ET (pg/mg) content in each group
Control group Saline group DSP group ET 149.091 .+-. 247.096 .+-.
116** 149.291 .+-. 19.537 41.865*# Notes: Comparison with control
group, *p > 0.05 **p < 0.001 Comparison with saline group, #P
< 0.05
[0649] The above experiment shows that blood plasma ET content
increases significantly in acute pancreatitis with malfunction of
multiple organs. Blood plasma ET content decreases significantly
after DSP treatment, and treatment can greatly improve liver,
kidney and pancreas function.
[0650] 8. Prevention of Platelet Aggregation and Thrombosis
[0651] 1. Effects on platelet aggregation in rats. Male rats
weighing about 300 g were anesthetized with 3% pentobarbital sodium
i.p. 1 ml of blood were collected from the carotid artery and
centrifuged. Platelet Rich Plasma (PRP) and Platelet Poor Plasma
(PPP) were collected. ADP was added into PRP, and platelet
aggregation percentage was tested after 5 mins, as shown in Table
8.1.
53TABLE 8.1 Effects of ADP on platelet aggregation Dosage Average
aggregation Aggregation Group (g/kg) Case percentage (X .+-. SD)
inhibition % Control Standard 31 66.74 .+-. 2.04 group solution DSP
0.4 14 35.09 .+-. 2.55 48.12 Tongmailing 0.2 10 53.10 .+-. 2.75
21.74 Xuesaitong 0.4 11 48.29 .+-. 5.5 24.54
[0652] 3. Effects on experimental thrombosis in rats. The Umetsu
method is used to carry out the experiment. The results in Table
8.2 show that high-dosage DSP (100 mg/kg) can significantly control
thrombosis, and low-dosage DSP (50 mg/kg) gives no significant
effects.
54TABLE 8.2 Effects on experimental thrombo-formation in rats
Average aggregation Dosage percentage Group (g/kg) Case (X .+-. SD)
Inhibition % Control Normal 10 21.8 .+-. 2.4 saline Aspirin 30 10
10.6 .+-. 2.1* 49.2 DSP 50 10 21.2 .+-. 2.9 6.5 100 10 11.7 .+-.
2.6* 44.8 Notes: Comparison with normal control group, *P <
0.01
[0653] 5. Effects on cAMP content in rabbit blood platelets. cAMP
content is tested by radioimmunoassay. Protein content is measured
by the Hartree Method. The results in Table 8.3 show that cAMP
content in blood platelets in the high-dosage (100 mg/kg) DSP group
increased more significantly than in the control group. The
low-dosage group (50 mg/kg) showed no significant effects.
55TABLE 8.3 Effects on cAMP content in rabbit platelets (X .+-. SD)
Group Dosage (mg/kg) Case (cAMP) Protein (Pmol/mg) Control Normal
Saline 15 6.2 .+-. 2.1 Aminophylline 0.6 20 15.4 .+-. 3.9* DSP 1.0
20 8.7 .+-. 3.2 2.0 10 13.6 .+-. 2.5* Notes: Comparison with
control group *P < 0.01
[0654] 6. Effects on cAMP content in rat blood plasma. Blood cAMP
content was tested by radioimmunoassay. The results show as table
8.4 that compared with the normal control group, blood plasma cAMP
content 30 mins and 60 mins after treatment increased in the
high-dosage DSP group (100 mg/kg). The low-dosage DSP (50 mg/kg)
group showed no significant effects.
56TABLE 8.4 Effects on blood plasma cAMP content (X .+-. SD) cAMP
content (Pmol/ml plasma) dosage Number of 30 min after 60 min after
Group (mg/kg) animals treatment treatment Control Normal 10 11.8
.+-. 3.6 11.4 .+-. 3.2 saline Amino- 30 10 20.7 .+-. 3.2 21.1 .+-.
3.8 phylline DSP 50 10 13.4 .+-. 4.1 13.3 .+-. 3.3 100 10 18.4 .+-.
2.9 17.6 .+-. 3.1 Notes: Comparison with normal control group at
the same times, *P < 0.01
[0655] Conclusion
[0656] The increasing of cAMP inhibits the activity of
phosphoesterase and epoxidase, and reduces the production of
prostaglandin peroxide. It can also activate protease to
phosphoesterize the membrane protein, alter the effects of membrane
protein composition on platelet aggregation, and control platelet
aggregation to prevent thrombosis. DSP can increase blood platelet
concentration and plasma camp content in order to prevent
thrombosis.
[0657] 9. Effects of DSP on Blood Vessels and Nerve Lesion in
Diabetic Rats
[0658] Method. 38 SD rats are divided into normal control group,
model group and DSP group, at random. The diabetic rat model is
made by abdominally injecting STZ60 mg/kg. DSP (0.25/kg.d.sup.-1)
was mixed into the normal feeding of the DSP group. The model group
and normal control group were given normal feedings. The experiment
lasted for 6 months. Total cholesterol (TC), High density
Lipoprotein-c (HDL-c), and Low-density lipoprotein-c (LDL-c) were
measured using U.S. Berer testing. Triglycerides (TG) used
acetylacetone colorimetry. The Plasma Nitrogen Monoxide (NO) was
measured by Fluorescence Spectrophotometry, and Propandiol (MDA)
was measured by TBA colorimetry. (GSH-PX) used the DTNB method.
Tissue-type plasminogen activator (t-PA), plasminogen activator
inhibitor (PAI), DD, FDP were tested by enzyme linked immunosorbent
assay. Insulin Radioimmunoassay and Glycated Hemoglobin
(HbA.sub.1c) were measured by high-performance liquid
chromatography. Contraves low share 30 was used to test blood flow
(made in Switzerland).
[0659] Results. After 6 months, the protein content of the 24-hr
DSP group was much lower (45% lower) than that of the model group
(P<0.001) Uric acid (UA) dropped at the same time (P<0.001),
but there was a significant difference between the two groups as
far as blood serum creatinine (Scr), blood serum urea nitrogen
(BUM) and urine volume (P>0.05), as shown in Table 9.1. The PAI,
DD and FDP of the model group and DSP group were much higher than
that of the normal control group (P<0.001). t-Pa was lower than
that of the normal control group, too (P<0.001). When compared
with the model group, the t-PA of the DSP group rose significantly
(P<0.001), and PAI, DD and FDP dropped (P<0.001), as shown in
Table 9.2. The TG, TC, HDL-c, NO, and MDA content and GSH-PX
activity of the DSP group were similar to that of the model group
(P>0.05).
[0660] Conclusion. DSP cannot thoroughly protect blood vessels and
nerves or prevent the occurrence of blood vessel and nerve lesion
in diabetic rats, but it can relieve or reduce its occurrence in
the 6 months-diabetic rat, especially in terms of protein in the
urine and lesion of blood capillaries of the kidneys and retina.
This may be related to the function of DSP, which can increase
thrombolysis.
57TABLE 9.1 Changes and comparison of function of kidneys in each
group after 6 months Volume 24 h Scr BUN UA of urine Protein n
(mg/dl) (mg/dl) (mg/dl) (ml) (mg) Normal 10 0.76 .+-. 0.219 17.3
.+-. 3.24 1.79 .+-. 0.326 13.6 .+-. 5.03 11.41 .+-. 4.04 Control
group Model 7 0.72 .+-. 0.075 35.6 .+-. 15.5# 3.47 .+-. 0.903*
155.8 .+-. 29.8.sup..quadrature. 111.7 .+-. 23.845.sup..quadrature.
group DSP group 7 0.73 .+-. 0.087 31.98 .+-. 11.45* 2.66 .+-.
1.04#.sup..DELTA. 145.3 .+-. 25.41.sup..quadrature. 50.5 .+-.
28.24.sup..DELTA.* Notes: Comparison with normal control group,
.sup..quadrature.P < 0.001, *P < 0.01, #P < 0.05;
Comparison with model group, .sup..DELTA.P < 0.001
[0661]
58TABLE 9.2 Changes and comparison of t-PA, PA, DD and FDP in each
group n t-PA (IU/ml) PAI (IU/ml) DD (mg/l) FDP (ug/ml) Normal 10
0.579 .+-. 0.033 0.748 .+-. 0.026 0.42 .+-. 0.048 4.645 .+-. 0.33
control group Model 7 0.186 .+-. 0.011* 0.898 .+-. 0.02* 0.714 .+-.
0.018* 6.667 .+-. 0.087* group DSP 7 0.255 .+-. 0.011*# 0.855 .+-.
0.014*# 0.532 .+-. 0.077*# 5.643 .+-. 0.037*# group Notes:
Comparison with normal control group, *P < 0.001; comparison
with model group, #P < 0.001
[0662]
59TABLE 9.3 Comparison of endogenous and patrolling cells in the
retina and their ratio after DSP treatment Endogenous Patrolling n
cells cells E/P Normal 10 667 .+-. 40.855 333 .+-. 40.741 2.042
.+-. 0.394 group Model 7 861 .+-. 43.760.sup..tangle-solidup. 138
.+-. 43.760.sup..tangle-solidup. 6.829 .+-.
2.246.sup..tangle-solidup. group DSP group 7 737 .+-.
32.408.sup..DELTA.# 262 .+-. 32.408.sup..DELTA.# 2.864 .+-.
0.533.sup..box-solid.* Notes: Comparison with normal control group,
.sup..tangle-solidup.P < 0.001, #P < 0.01, .sup..box-solid.P
< 0.001; comparison with model group, .sup..DELTA.P < 0.001
*P < 0.001 In conclusion, DSP can increase blood flow to the
coronary artery; relax the smooth muscles in blood vessels;
activate peripheral circulation; raise venous oxygen content;
significantly improve acute myocardial infarction; reduce apoptosis
by interfering with Fas/FasL protein expression to protect the
cells from damage
[0663] by hypoxia and deoxygenation/re-oxygenation; improve
circulation; and protect myocardial tissue. It can also prevent
cardiac arrhythmia and platelets aggregation; activate
thrombolysis; reduce blood viscosity; adjust lipoprotein levels;
prevent atherosclerosis; increase tolerence to hypoxia; prevent
oxidation of fats; remove harmful free radicals; reduce ET content
in blood plasma; and improve the liver, kidney and pancreas
function to prevent the occurrence of blood vessel and nerve
lesion.
[0664] Clinical Research on Dan Shen Pill
[0665] 1. Treatment of Coronary Heart Disease with DSP
[0666] (1) Ordinary Treatment of Coronary Heart Disease with
DSP
[0667] After DSP came onto the market in China, a large-scale
clinical research project was conducted in China. Although
different prescriptions were used in different research projects,
all conclusions are written according to "Method of DSP clinic
study." All clinical and experimental markers were standardized. A
simplified summary of the results is shown below in Table 1-1.
60TABLE 1-1 Clinical conclusion of effects of DSP on treatment of
coronary heart disease and angina Clinical Name of hospital Case
efficacy % ECG-Efficacy % Normal control.sup.(1) Huabei Chinese
Hospital 80 87.5 -- -- Shan Dong Weifang 162 86.6 70.7 -- Hospital
Zhejiang hospital of 100 96** -- DSP(50; 92%; --) Traditional
Chinese Medicine Affiliated Hospital 98 93.9 58.3 -- Hunan College
of TCM Guangzhou Hospital of TCM 100 96** 63* DSP(30; 63.3%; 30%)
Tangshan Hospital of TCM 101 95.1 60.4 Isordil(48; [84.2]** [46.5]*
79.2%; 37.5%) [87.5%; 43.8%] Affiliated Hospital 46 95.7* 76.1*
Nifedipine(32; 75%; Anhui College of TCM 43.8%) Hunan Shuangfeng 32
--.sup.(2) 82.4** Isordil(31; --; 74.5% Hospital Shanxi Provincial
97 78.4* 41.5 DSP(41; 65.9%; 32.3%) Hospital Jingxi Hospital, 4th
39 92.4 79.5 -- Medicine University Guangzhou Hospital of TCM 120
92.5 60 -- Shenyang Seventh 62 93.5 74.2 Isordil(30; Hospital
72.5%; 60%) Guangdong Affiliated 30 66.7 -- Isordil(23; Hosp. of
TCM 69.6%) Guang'anmen Research 40 92.5 60 Isordil(20; Institute of
TCM 90%; 55%) Tianjin First Hospital 128 82.8 -- -- Affiliated
Hospital of 102 [88.3] [37.3] Glyceryl Anhui College of TCM
trinitrate(30; [93.3%; 40%]) The 1st Affiliated 34 --.sup.(3)** --
Isordil (30) Hospital, Hebei Medicine College Tianjin Huanhu
Hospital 58 96.5* 53.5 DSP(152; 75.1%; 46.2%) Fujian Provincial 100
96 89.1 -- Hospital Changzhou Hospital in 43 95.3** 62.8** DSP(43;
74.4%; Jiangshu Province 37.5%) Shanxi Research 206 92 63.6 --
Institute of Traditional Chinese Medicine Xintai Hospital in 60
96.7** 63.3 DSP(30; 76.6%; Hebei Province 43%) The 1st Affiliated
30 83.3 56.6 -- Hospital of Shanghai Medicine University Henan
Dianli Hospital 90 91.1 60 -- Jinan Provincial Hospital 60 76.7*
61.7** Isordil(30; 53.3%; 36.7) Xi'an Military Hospital 87
96.sup.(4) 64.6 Glyceryl trinitrate(87.sup.(4)) Total 2105 90.06
61.8 Note: The numbers inside the [ ] represent the pain-killing
function and improvement in ECG results. Comparison with normal
control group, *p < 0.05; **p < 0.01 .sup.(1)Numbers in the (
) in order of appearance are: sample number, angina improvement
after treatment and percentage improvement in ECG after treatment.
.sup.(2)The standard markers were cardiac output (CO), stroke
volume (SV), Ejection fractin(EF), (FS), .beta. platelet
microglobulin, Thromboxane .beta..sub.2, Holter Test for ST-T
changing times, etc. .sup.(3)The standard markers were Heart
Ratio(HR), systolic pressure (SBP), (Product), diastolic
pressure(DBF), output(SV) per pulse, cardiac output (CO), cardiac
Index(CI), ejection fration(EF), angina onset frequency, and dosage
of glyceryl trinitrate. .sup.(4)This was a cross companion test, so
there is no statistical difference between the medicine in the
angina group and in the ECG group.
[0668] According to Table 1-1, the effects of DSP on the treatment
of coronary heart disease are much better than that of DSS,
statistically. The treatment is basically similar to that of
Isordil and there is no significant difference between them
statistically. DSP is a pure Chinese medicine. It works efficiently
in small dosages. It is convenient, safe, easily-absorbed, and has
no side effects.
[0669] (2) Pain-Killing Effects of DSP on Coronary Heart Disease
Compared with Glyceryl Trinitrate. The Pain-Killing Function of DSP
for Coronary Heart Disease is Discussed.
[0670] 1. Example. 132 patients with coronary heart diseases were
selected. They were divided into 2 random groups, 102 patients in
the treatment group and 30 patients in the control group. They were
classified according to Chinese Medical Method into: 42 patients in
the Qizhi Xueyu treatment group, 24 patients in the Tanshi Bizhu
treatment group, 7 patients in the Yangxu Hanning treatment group,
29 patients in the Qiyin Liangxu and Xueyu treatment group; and 11,
7, 2, and 10 patients, respectively, were assigned to the control
groups.
[0671] 2. Method. An ECG was conducted once before the pain begins.
Patients in the treatment group took 10 DSP during the pain, while
those in the control group took 0.5 mg glyceryl trinitrate. The
time it took for the pain to end was recorded and used as a
reference. An ECG was conducted again 30 mins after treatment and
compared it with the one taken before.
[0672] 3. Standard. Three pain-killing standards were established:
obvious effectiveness--pain ended 3 minutes after treatment;
effectiveness--pain ended 3.about.8 minutes after treatment; and
Failure-pain ended 8 hrs or more after treatment.
[0673] Results
[0674] (1) Speedy Painkilling. The obvious effectiveness of the
treatment group was 40.20%, and the total efficacy was 88.28%. The
obvious effectiveness of the control group was 53.33%, and total
efficacy was 93.33%. There was no significant difference between
the two groups (P>0.05). These two groups have a similar
treatment effect on coronary heart diseases, as shown in Table
1-2.
61TABLE 1-2 Efficacy of painkilling Case Obvious Total Group No.
Efficacy (%) Efficacy (%) Failure (%) efficacy (%) Treat- 102 41
(40.20) 49 (48.04) 12 (11.76) 90 (88.24) ment Control 30 16 (53.33)
12 (40.00) 2 (6.67) 28 (93.33)
[0675] (2) Using ECGs to compare treatment results, the obvious
efficacy in the treatment group was 15.69%. The total efficacy was
37.26%. The obvious efficacy in the control group was 20%, and
total efficacy was 40%. There was no significant difference between
the groups (P>0.05), as shown in Table 1-3.
62TABLE 1-3 Efficency on ECG After Dosage Case Obvious Total Group
No. Efficacy (%) Efficacy (%) Failure (%) efficacy(%) Treat- 102 16
(15.69) 22 (21.57) 64 (62.74) 38 (37.26) ment Control 30 6 (20.00)
6 (20.00) 18 (60.00) 12 (40.00)
[0676] (3) There is a close relationship between Chinese
Classification of Coronary Heart Disease and the efficacy in the
treatment group, as shown in Table 1-4. It shows that DSP has the
identical treatment efficacy on the different categories of heart
pain classified by Chinese medicine.
63TABLE 1-4 Efficacy in the treatment group in Traditional Chinese
Medicine Classification of Coronary Heart Disease Obvious Total
Group Cases Efficacy (%) Efficacy (%) Failure (%) efficacy (%)
Qizhi 42 18 (42.86) 19 (45.24) 5 (11.90) 37 (88.10) Xueyu Tangshi
24 7 (29.17) 14 (58.33) 3 (12.50) 21 (87.50) Bozhu Yinshi 7 4
(57.14) 2 (28.57) 1 (14.29) 6 (85.71) Hanling Qiyin Liangxu 29 12
(41.38) 14 (48.28) 3 (10.34) 26 (89.66) And Xueyu
[0677] Conclusion
[0678] The above experiment shows that the effects of DSP treatment
on for coronary heart disease is similar to that of glyceryl
trinitrate. The results of both ECGs are similar 30 mins after
treatment, and the Chinese classification of coronary heart disease
does not affect the efficacy of DSP.
[0679] (3) Effects of DSP on the Onset of Coronary Heart Disease,
Heart Pain Frequency and Volume of Glyceryl Trinitrate Used.
[0680] 1. Sample selection. Samples were selected according to WHO
clinical standards. Patients must have exhibited least
exertion-related angina pectoris for 3 months. Onset frequency was
more than 5 times a week with positive results in exercise tests
and pain relieved by rest or oral glyceryl trinitrate. The total
number in the sample was 64.
[0681] 2. Method of research. The research was divided into two
periods at random using the double-blind method. The first period
(cleansing period) lasted 2 weeks. All medications except for
glyceryl trinitrate were stopped. The second period lasted 8 weeks,
and 10-15 DSP were given to one group, 3 times per week, while
10-15 mg of Isordil was given to another group, 3 times a week.
[0682] 3. Results. Onset frequency of the DSP-protected group
decreased from 1.93.+-.3.10 to 0.48.+-.1.33 with a statistical
error of P<0.01. The volume of glyceryl trinitrate used
decreased from 1.88.+-.2.96 tablets per day to 0.51.+-.1.44 tablets
per day with a significant difference (P<0.01), as shown in
Table 1-5.
64TABLE 1-5 Changes in onset frequency and volume of glyceryl
trinitrate used DSP group (n = 34) Isordil group (n = 30) Before
treatment After treatment Before treatment After treatment Onset
Frequency 1.93 .+-. 3.10 0.48 .+-. 1.33**## 1.91 .+-. 2.44 1.64
.+-. 1.62* (times/day) glyceryl trinitrate 1.88 .+-. 2.96 0.51 .+-.
1.44**## 1.86 .+-. 4.51 1.64 .+-. 1.46* used (tablet/day) Notes:
Comparison before and after treatment, *P < 0.05 **P < 0.01,
Comparison between the 2 groups, ##P < 0.01
[0683] The results show that DSP can reduce onset frequency and
volume of glyceryl trinitrate used. The level and duration of pain
improved after a certain period of treatment, and the onset
frequency also decreased. This explains why DSP can improve blood
flow to the heart in addition to relieving pain.
[0684] (4) Improvement of blood pressure and cardiac function in
patients with coronary heart disease. Method of sample selection
and the method of research are the same as (3).
[0685] The results are shown in Tables 1-6 and 1-7. They prove that
DSP can improve cardiac function in patients with coronary heart
disease and provide improvements in blood flow.
65TABLE 1-6 Changes in heart rete, blood pressure, and
corresponding product in DSP treatment and Isordil treatment index
DSP group (n = 34) Isordil group (n = 30) Before After Before After
Marker treatment treatment treatment treatment SBP (Kpa) 24.5 .+-.
2.1 23.2 .+-. 1.4**## 23.9 .+-. 4.1 24.8 .+-. 1.1 DBP (Kpa) 11.8
.+-. 4.1 11.1 .+-. 2.1**## 11.8 .+-. 3.2 12.1 .+-. 2.1
Corresponding 24399 18932**## 24399 26203 product Notes: Comparison
before and after treatment by matching t statistic testing: **P
< 0.01, Comparison between the 2 groups, ##P < 0.01
[0686]
66TABLE 1-7 Changes in blood flow indexes after DSP treatment and
Isordil treatment DSP group (n = 34) Isordil group (n = 30) Before
After Before After Markers treatment treatment treatment treatment
PAP (mmHg) 34.4 .+-. 6.1 27.4 .+-. 8.8 34.8 .+-. 5.1 33.9 .+-. 6.6
PCWP (mmKg) 34.8 .+-. 9.1 24.3 .+-. 6.7 32.6 .+-. 8.1 31.1 .+-. 5.1
CO (L/min) 2.81 .+-. 0.4 4.64 .+-. 1.1 3.81 .+-. 0.1 3.89 .+-. 1.1
CI (I min.sup.-1/m.sup.2) 3.47 .+-. 1.1 3.89 .+-. 0.3 3.51 .+-. 1.0
3.58 .+-. 1.6 EF (%) 76 .+-. 11 74 .+-. 16 77 .+-. 14 78 .+-. 11
Notes: Comparison before and after treatment by matching t
statistic testing: *P < 0.05 **P < 0.01, Comparison between
the two groups, #P < 0.05 ##P < 0.01
[0687] (5) Effects of DSP on ECGs and blood flow in patients with
coronary heart disease
[0688] By comparing DSP and well-known pain medication Isordil,
DSP's clinical treatment effects and toxic side effects are
discussed.
[0689] 1. Objects and Methods
[0690] 1.1 Sample. The total number of patients with steady angina
pectoris was 109. They all qualified under WHO Standard Cardiac
function Category I.about.II, 1979. They were divided into two
groups at random: 57 in the treatment group and 52 in the Isordil
group (control group).
[0691] 1.2 Method. All patients stopped taking all myocardial
ischemia medications for five half-lives before beginning
treatment. Patients with coronary heart disease were given oral
glyceryl trinitrate temporarily. The treatment group was given DSP,
while the control group was given Isordil (Shanghai Medical
University Red Flag Medicine Factory), 10-15 mg/time, 3 times/day.
Medication was taken for 4 weeks.
[0692] 1.3 Recording Standards. Onset frequency, body parts, level
of pain, heartbeat, blood pressure, duration, onset factors,
consumption of glyceryl trinitrate, time it takes for the medicine
to begin functioning, Movable Plane Exercise Test results, and
blood flow.
[0693] 1.4 Treatment standard:
[0694] 1.4.1 Symptom standards. (a) Obvious Efficacy: The same
level of fatigue did not trigger onset of pain, or onset frequency
decreased by more than 90 percent. Glyceryl trinitrate was not
used. (b) Efficacy: Onset frequency and amount of glyceryl
trinitrate used decreased 0-90%. (c) Failure: The above standards
could not be reached. (d) Worsening: Onset frequency and amount of
glyceryl trinitrate used increased 50% or more.
[0695] 1.4.2 ECG standards: (a) Obvious Efficacy: The result of the
Movable Plane Exercise Test changed from positive to negative, or
exercise tolerance increased to .gtoreq.grade 2. (b) Efficacy:
Movable Plane Exercise Test ECG ischemia ST segment rebounded to
.gtoreq.1.5 mm, or exercise tolerance increased 1 grade (c)
Failure: The above standards were not reached.
[0696] Results
[0697] 2.1 Observation of symptomic efficacy. See Table 1-8. Total
efficacy: treatment group 93.0%; control group 86.5%. No
significant difference between the two groups (P>0.05).
[0698] 2.2 Observation of ECG efficacy: See Table 1-9 and Table
1-10. The Onset of angina without exercise and onset of angina with
exercise for section ST decreased .gtoreq.0.1 mv in the 2 groups
after treatment. There were improvements in the greatest decreasing
value of section ST and the greatest payload, but there is no
significant difference between them (P>0.05). All standards in
the treatment group improved both before and after treatment
(P<0.01).
[0699] 2.3 Observations on blood flow were shown in Table 1-11. All
standards in the treatment group have improved after treatment
(P<0.01), but there was no difference in those of the control
group (P>0.05). Significant differences in blood flow were found
between the two groups (P<0.01). This shows that DSP can improve
blood flow.
67TABLE 1-8 Comparison of the symptoms in the two groups before and
after treatment Results Total Obvious Worsening efficacy Group
Cases Efficacy Efficacy Failure cases (%) DSP 57 32 21 3 1 93.0*
Isordil 52 28 17 5 2 86.5 Notes: Comparison with the control group,
*P > 0.05
[0700]
68TABLE 1-9 Comparison of the ECG in the two groups before and
after treatment Results Obvious Worsening Total Group Cases
Efficacy Efficacy Failure case efficacy (%) DSP 49 19 11 18 1 61.4*
Isordil 47 16 12 17 2 59.6 Notes: Comparison with the control
group, *P > 0.05
[0701]
69TABLE 1-10 Changes in Movable Plane Exercise indexes before and
after treatment Time for Exercise section ST required for The
greatest trigger 0.1 mV lower Section ST The lowest of payload
Group Cases time (sec.) 0.1 mV lower (MET) section ST (mm) (METS)
DSP 49 Before 228 .+-. 60 204 .+-. 79 4.2 .+-. 2.0 2.5 .+-. 1.8 7.3
.+-. 1.2 treatment After 301 .+-. 94* 268 .+-. 92* 5.6 .+-. 2.3*
1.8 .+-. 1.1* 9.8 .+-. 2.1* treatment Isordil 47 Before 230 .+-. 39
210 .+-. 76 4.5 .+-. 1.8 2.2 .+-. 0.9 7.8 .+-. 1.6 treatment After
303 .+-. 89 257 .+-. 85 5.8 .+-. 2.6 1.6 .+-. 0.8 10.1 .+-. 2.2
treatment Notes: *Comparison with this group before treatment, P
< 0.01; Comparison with control group after treatment, P >
0.05.
[0702]
70TABLE 1-11 Changes in blood flow indexes in the two groups before
and after treatment Length of Sedimentation Blood platelet
exogenous Whole blood Blood plasma equation viscosity thrombin
Group Cases Viscosity viscosity value K percentage (%) (mm) DSP 52
Before 5.31 .+-. 0.89 1.83 .+-. 0.86 103.78 .+-. 12.68 30.25 .+-.
7.84 18.5 .+-. 3.0 treatment After 4.67 .+-. 0.71* 1.35 .+-. 0.92*
96.45 .+-. 10.21* 25.30 .+-. 5.90* 16.0 .+-. 3.1* treatment Isordil
50 Before 5.33 .+-. 0.93 1.81 .+-. 0.81 105.15 .+-. 12.68 30.75
.+-. 6.93 18.2 .+-. 2.7 treatment After 5.20 .+-. 0.96 1.80 .+-.
0.68 102.26 .+-. 12.11 29.10 .+-. 8.50 18.0 .+-. 2.4 treatment
Notes: *Comparison with this group before treatment, P < 0.01;
Comparison with control group after treatment. P < 0.01
Self-matching t test before and after treatment: *P > 0.05. t
test in 2 groups: ** P > 0.05
[0703] Conclusion
[0704] No significant differences appeared on ECGs and average
exercise testing standards to show improvement from DSP and Isordil
(P>0.05), but the average exercise testing standards in the DSP
group were much better before and after treatment (P<0.01). This
test proves that the treatment effects of DSP on coronary heart
disease are the same as that of Isordil with no side effects and
increase in tolerence. Also, DSP controls irregular blood flow,
lowers blood viscosity, reduces the occurence of atherosclerosis,
and prevents thrombosis much better than Isordil and can be the
first choice for the treatment of coronary heart disease.
[0705] (6) Effects of long-term DSP treatment on coronary heart
disease The effects of long-term DSP treatment on coronary heart
disease in comparison to Isordil are discussed.
[0706] 1. Subjects. 40 patients with stable-type angina are
selected, and divided into two groups at random, 20 in the
treatment group (DSP group) and 20 in the control group (Isordil
group.
[0707] 2. Method. Patients are medicated and observed using
double-blind method. The DSP group takes 10 tablets/day, 3
times/day, and the Isordil group takes 10 mg, 3 times/day.
[0708] Results
[0709] 1. Efficacy. There was difference after 2 weeks of
medication. The results were 90% vs 75% (P>0.05, 90% vs 70%
(P<0.05), 95% vs 65% (P<0.01) in 4, 6 and 8 weeks
respectively with the DSP group showing results superior to that of
the control group.
[0710] 2. Electrocardiography (ECG) Efficacy: There was difference
between the two groups after 2 weeks of medication. The results
were 80% vs 65% (P<0.05), 75% vs 55% (P<0.05), 80% vs 50%
(P<0.08) at 4, 6 and 8 weeks, respectively, with the DSP group
showing results superior to that of the control group (Table
1-12).
71TABLE 1-12 Comparison of treatment efficacy based on ECG results
2 weeks 4 weeks 6 weeks 8 weeks Results DSP Isordil DSP Isordil DSP
Isordil DSP Isordil Efficacy Obvious 5 (25.0) 6 (30.0) 6 (30.0) 5
(25.0) 6 (30.0) 4 (20.0) 7 (35.0) 3 (15.0) of angina Efficacy
pectoris Efficacy 12 (60.0) 12 (60.0) 12 (60.0) 10 (50.0) 12 (60.0)
10 (50.0) 12 (60.0) 10 (50.0) (%) Failure 3 (15.0) 2 (10.0) 2
(10.0) 5 (25.0) 2 (10.0) 5 (25.0) 0 (0) 5 (25.0) Worsen 0 (0) 0 (0)
0 (0) 0 (0) 0 (0) 1 (5.0) 1 (5.0) 2 (10.0) cases Efficacy 17 (85.0)
18 (90.0) 18 (90.0) 15 (75.0) 18 (90.0) *14 (70.0) **19 (95.0) 13
(65.0) rate P value >0.05 <0.05 <0.05 <0.01 Efficacy
Obvious 4 (20.0) 4 (20.0) 5 (25.0) 3 (15.0) 5 (25.0) 3 (15.0) 6
(30.0) 2 (10.0) of ECG Efficacy (%) Efficacy 10 (50.0) 11 (55.0) 11
(55.0) 10 (50.0) 10 (50.0) 8 (40.0) 10 (50.0) 8 (40.0) Failure 6
(30.0) 5 (25.0) 4 (20.0) 5 (25.0) 4 (20.0) 7 (35.0) 3 (15.0) 7
(35.0) Worsen 0 (0) 0 (0) 0 (0) 2 (10.0) 1 (5.0) 2 (10.0) 1 (5.0) 3
(15.0) cases Efficacy 14 (70.0) 15 (75.0) 16 (80.0) 13 (65.0) 15
(75.0) *11 (55.0) **16 (80.0) 10 (50.0) rate P value >0.05
<0.05 <0.05 <0.01 Notes: Comparison at 6 weeks and 2 weeks
on medication: DSP group *P > 0.05; Control group **P <
0.05
[0711] Conclusion
[0712] Long-term DSP treatment is more efficient and yields better
ECG results than Isordil treatment. The results are stable, and
there is no antibiotic resistance. Isordil can efficiently lower
blood pressure, leading to the activation of endogenous nerve and
body fluid system and an increase in blood volume. In addition,
Isordil works on sulfur radicals inside the capillary wall, but it
would consume sulfur radicals in the long term and reduce treatment
effects. DSP is a multi-level, multi-subjected and multi-method
medicine which improve cardiac muscle, increases blood volume by
blocking the chronic calcium route; stabilizes the myocardial
membrane; removes free radials; regulates myocardial cells
metabolism; improves blood platelets aggregation; and lowers
cholesterol and blood viscosity. Therefore, long-term DSP treatment
gives significant treatment effects.
[0713] (7) Treatment of Unstable-Type Angina
[0714] Clinical research on the effects of DSP on unstable-type
angina.
[0715] 1. Subjects and Methods
[0716] 1.2 Sample: 65 patients with unstable-type angina were
divided into two groups at random: 34 in the treatment group, which
includes 22 males and 12 females; 31 in the control group which
includes 20 males and 11 females.
[0717] 1.3 Method. Two groups of patients were injected normally
with 30 ml of DSP, Qd, 80 mg oral aspirin, Qd. Patients in the
treatment group were given DSP, 10 tablets/day, 3 times/day;
Isordil was given to those in the control group, 10 mg/time, 3
times/day. The medication lasted for 20 days. No coronary
artery-dilating and fat-lowering drugs were given. If pain
worsened, glyceryl trinitrate was given.
[0718] Results
[0719] 1. Comparison of results. In the treatment group, the number
of obvious efficacy, efficacy, failure and worsening cases were
26%, 6%, 2%, 0, respectively, and the total efficacy was 94.1%. In
the control group, the results were 15%, 8%, 6%, 2%, respectively,
and the total efficacy was 74.2%. The results of both groups were
classified under the Ridit statistic testing Method
(P<0.05).
[0720] 2. Comparison of coronary heart disease classifications
before treatment. Patients exhibiting low, medium, low-medium and
high symptoms according to the Ridit statistic testing Method
(P<0.05) in the treatment group were 27, 4, 2, and 1,
respectively. Those in the control group were 14, 9, 7, and 1,
respectively.
[0721] 3.. Comparison of ECGs: the total efficacy in the treatment
group was 61.7%, and that-of the control group was 41.94%. There
was a significant difference in the efficiencies of the two
groups.
[0722] 4. Treatment of related symptoms. Related symptoms include
palpitation, a suffocation of sense, oral cyanosis. After
treatment, there was a more significant difference in the number of
patients suffering from a sense of suffocation, oral cyanosis and
ecchymosis in the treatment group than in the control group
(P<0.01). However, there was no difference in palpitation
(P<0.05).
[0723] 5. For change in blood flow. See Table 1-13.
72TABLE 1-13 Change in blood flow Experimental group Control group
Before After Before After Standards treatment treatment treatment
treatment Whole blood 4.91 .+-. 0.42 4.02 .+-. 0.32*.sup..DELTA.
4.86 .+-. 0.38 4.56 .+-. 0.41 viscosity (cp) Erythrocyte 49.20 .+-.
2.74 42.28 .+-. 2.12* .sup. 52.00 .+-. 2.52 48.53 .+-. 2.13
hematocrit (%) Blood 24.65 .+-. 9.76 22.18 .+-. 8.23.sup. 25.10
.+-. 9.34 22.30 .+-. 8.17 sedimentation (mm/h) Fibrinogen 487.50
.+-. 85.14 .sup. 403.33 .+-. 91.15**.sup..DELTA..DELTA. 494.33 .+-.
86.02 487.00 .+-. 89.61 (mg %) Notes: Comparison with this group
before treatment, *P < 0.05; Comparison with control group,
.sup..DELTA.P < 0.05, .sup..DELTA..DELTA.P < 0.01
[0724] Conclusion
[0725] The above experiment shows that DSP can reduce oxygen
consumption by cardiac muscles, improve blood flow in coronary
arteries, rebalance oxygen demand-to-oxygen supply ratio in cardiac
muscles.
[0726] The effects of DSP on treatment of exertion-type of angina
on 60 additional patients.
[0727] 1. Sample selection. 60 patients in total, including 42
males and 18 females, aged 32-75, with an average age of 52.2, and
positive results in the Plane Exercise Test were selected.
[0728] 2. Method of medication. DSP was given, under lingua, 10
tablets/medication, 3 times/day. The medication lasted for 6
weeks.
[0729] 3. Results. Refer to the 1997 CHD Angina Standard.
[0730] (1) Efficacy. No occurrence of angina, 21 patients with
increased physical tolerance (35%), 15 patients with negative
results in the Plane Exercise Test (25%).
[0731] (2) Improvement. 29 patients with a two-thirds decrease in
the frequency of onset of pain or shortening of the duration of
pain (48.3%), 28 patients with suspicious positive results in the
Plane Exercise Test (46.5%).
[0732] (3) Failure. 10 patients had no change in onset frequency
and duration (16.7%). 17 patients had positive results in the Plane
Exercise Test (28.3%)
[0733] Conclusion
[0734] DSP can efficiently relieve pain and increase blood flow to
the cardiac muscle. DSP can also reduce oxygen consumption, improve
blood flow to the coronary artery, rebalance oxygen demand and
oxygen supply, and prevent atherosclerosis. It is the ideal
medicine for the prevention or treatment of coronary heart disease,
angina and atherosclerosis.
[0735] (8) Research on Senior Group Angina
[0736] Both DSP and Nifedipine can treat angina caused by coronary
heart disease, but the latter has side effects which are not
suitable for long-term use. In order to choose suitable drugs for
patients with a need for long-term treatment of coronary heart
disease, a comparative analysis of DSP and Nifedipine in the
treatment of angina caused by coronary heart disease was carried
out.
[0737] 1. Materials and Methods
[0738] 1.1 Subjects. 50 senior patients with coronary heart disease
were divided into two groups: 30 in the DSP group (Treatment
group),20 in the Nifedipine group (Control group). Patients in both
groups did not have significant differences in terms of sex, age,
medication, and Chinese medical classification, but a comparison of
the differences is worthwhile.
[0739] 1.2 Method. DSP was given to the Treatment group, 10-15
tablets/medication, 3 times/day; Nifedipine was given to the
Control group, 10.about.15 mg/medication, 3 times/day. Medications
were taken for 30 days. Patients in both groups used Yongbaoling
spray under their tongues during acute onset of symptoms. Other
medications with no obvious effects were used during the treatment
process.
[0740] 1.3 Types of tests. Onset frequency, duration, number of
times Yongbaoling was sprayed each day, 12-lead ECG, blood
pressure, heartbeat, normal blood urea, liver and kidneys function,
and lipoproteins in blood and blood viscosity both before and after
treatment.
[0741] 1.4 Statistical analysis. The results were measured by t
statistic testing, calculated by x.sup.2 statistic testing.
[0742] 2. Confirmation of results. Onset frequency and duration
with a decrease of 80% or more was regarded as obvious efficacy. A
decrease of 50% or more was regarded as efficacy. A decrease of 50%
or less was regarded as a failure. Changes in NST and .SIGMA.ST
before and after treatment were used to observe ECG improvement.
NST represented the low-pressure 12-lead numbers in section ST;
.SIGMA.ST represented the sum of all low pressure numbers in
section ST of 12-lead.
[0743] Results
[0744] Clinical results are shown in Table 1-14.
73TABLE 1-14 Comparison of clinical results of the two groups after
treatment (%) Sample Obvious Total Group number Efficacy Efficacy
Failure efficacy (%) With 30 19 (63.33) 8 (26.67) 3 (10.00) 90
treatment Control 20 8 (40.00) 4 (20.00) 8 (40.00) 60 Notes:
Comparison with control group, P < 0.05
[0745] 3.2 Change in ECG and number of times Yongbaoling was
sprayed per day is shown in Table 1-15.
74TABLE 1-15 Comparison of change of NST and .SIGMA.ST and usage of
Yongbaoling sprays Number of Sample Yongbaoling Group number NST
.SIGMA.ST sprays per day With Before treatment 30 4.21 .+-. 1.31
1.76 .+-. 0.87 3.1 .+-. 1.0 treatment After treatment 3.10 .+-.
1.21 1.05 .+-. 0.61 1.0 .+-. 0.5 Control Before treatment 20 4.20
.+-. 1.25 1.75 .+-. 0.85 3.21 .+-. 1.1 After treatment 3.90 .+-.
1.13 1.60 .+-. 0.71 2.2 .+-. 0.8 Notes: Comparison before and after
treatment, P < 0.05; Comparison between treatment group and
control group, P < 0.05.
[0746] 3.3 Side-effects: 3 patients in the Nifedipine group felt
pain, 2 had swollen ankles, 1 had slow heartbeat. There was no
damage to liver and kidney function, adverse gastrointestinal
reaction or cardiac arrhythmia in the treatment group.
[0747] Conclusion
[0748] DSP is made for angina. It activates blood circulation and
relieves pain efficiently. Its effects are long lasting, require
only a small dosage and have no side effects. Nifedipine is a
short-term-effective calcium antagonist with a short half-life and
functional time, so angina may occur during medication. It also has
many side effects. Many reports state that long-term treatment with
Nifedipine is harmful to coronary arteries. DSP can prevent
decreased blood flow to the cardiac muscles and the development of
atherosclerosis.
[0749] (9) Effects on Non-Symptomatic M-IR
[0750] 1. Clinical sample. 52 patients were in the treatment group,
which included 39 patients with coronary heart disease, and 4
patients with M-IR, and 9 patients with positive results on the
exercise test. There were 38 males and 14 females. 52 patients were
in the control group, which included 43 patients with coronary
heart disease, 6 patients with M-IR, and 3 patients with positive
results on the exercise test. There were 34 males and 18 females
(Both groups followed the WHO M-IR-Related Heart Disease and
Standard established in 1979).
[0751] 2. Method of treatment. DSP was given to the treatment
group, 10 tablets/medication, 3 times/day. Nifedipine was given to
the control group, 10 mg/medication, 3 times/day. Both medications
lasted for 4 weeks, and all medications related to the treatment of
M-IR were stopped.
[0752] 3. Result standard. Efficient: Change of ECG ST-T was close
to normal; Better: Decreased section ST rose 0.5 mm or more,
transverse wave T changed to vertical ones, inverted wave changed
25% or more, conducting resistance was improved; Failure: There was
no difference in ECGs before and after treatment.
[0753] Results
[0754] (1) Efficacy in both the DSP group and the Nifedipine
control group increased as treatment progressed, as shown in Table
1-16. There was a significant difference between the groups
(P<o. 01)
75TABLE 1-16 Efficient dynamic changes in 2 groups after treatment
Group 1.sup.st week 2.sup.nd week 3.sup.rd week 4.sup.th week With
Obvious 12 17 21 22 treatment Efficacy (n = 52) (Number) Efficacy
10 13 15 17 (Number) Efficacy 42.3 57.7 69.2 75.0 (%) Control
Obvious 8 10 11 12 (n = 52) Efficacy (Number) Efficacy 5 6 7 8
(Number) Efficacy 25.0 30.8 34.6 38.5 (%)
[0755] (2) 24-hr dynamic ECG records showed that with DSP
treatment, the number and average duration of extrasystole in
patients decreased significantly from 5.37 min once before
treatment to 1.58 min once after it, a great difference before and
after treatment, as shown in Table 1-17.
76TABLE 1-17 Comparison of extrasystole frequency and duration in
dynamic ECG record before and after treatment Average time of
extrasystole Cumulative onset number time (min) (mins/counts)
Before 95 510 5.37 treatment After 24 38 1.58* treatment
[0756] All onset times for patients in this group shortened. No
toxic side effects were found. The drug is safe, suitable for
long-term use, and efficient. It shows advantages and potential for
broadening functions in the future.
[0757] 2. Effects on Cardiac Arrhythmia
[0758] (1) Treatment of Cardiac Arrhythmia
[0759] 1. Subject. 46 patients with coronary heart disease and
cardiac arrhythmia (including 39 males and 7 females) and 55
patients without heart disease but with cardiac arrhythmia
(including 36 males and 19 females) were chosen.
[0760] 2. Arrhythmia was confirmed by ECG and
electrocardio-monitoring. All heartbeat irregularity medication in
5 half-life periods was stopped before treatment. DSP was given at
doses of 10 tablets/medication, 3 times/day. ECG and arrhythmia are
checked after 2 weeks of medication.
[0761] Results
[0762] (1) Irregularity of heart rhythm in the coronary heart
disease group before treatment is shown in Table 2-1.
77TABLE 2-1 Comparison of irregularity of heart rhythm in the
coronary heart disease group before and after treatment Premature
Premature Sinus Premature atrioventric- ventric- Bundle- brady-
atrial ular juction ular branch cardia beats beats beats AVB block
Before 14 21 7 32 11 5 treat- ment After 3* 5** 2* 8** 4* 3 treat-
ment Notes: Comparison before and after treatment, *P < 0.05,
**P < 0.01. Few patients have different kinds of heart rhythm
irregularities at the same time.
[0763] (2) Irregularity of heart rhythm in control group before and
after treatment is shown in Table 2-2.
78TABLE 2-2 Irregularity of heart rhythm in control group before
and after treatment Premature atrio- Sinus Premature ventricular
Premature Bundle- brady- atrial juction ventricular branch cardia
beats beats beats AVB block Before 8 16 4 23 6 4 treatment After 2*
3** 2 9* 3 2 treatment Notes: Comparison before and after
treatment, *P < 0.05, **P < 0.01.
[0764] Conclusion
[0765] The treatment effects of DSP on cardiac arrhythmia caused by
coronary heart disease are significant. It is also helpful to those
patients without heart disease. Its functions are: a)
Calcification. DSP can reduce intracellular calcium concentration
and prevent calcium overloading better than verapamil. B)
Stabilizing the cell membrane. DSP can protect cardiac muscle and
regulate heart rhythm. c) Removal of free radicals. D) Speeding up
energy production and utilization. There is no relationship between
chronic irregularity of heart rhythm and the addition of resistance
and lack of energy supply.
[0766] (2) Long-Term Effects on Irregularity of Heart Rhythm Caused
by Myocarditis and Cardiac Functions
[0767] 1. Clinical samples. 120 patients with myocarditis were
selected according to Whole Country Myocarditis Conference
Standards, 1995. Patients took their own regular medication for one
month and then were randomly divided into two groups with 60
patients per group. The DSP group (Treatment group) included 33
males and 27 females. The Di'ao Xinxuekang group (Control group)
included 31 males and 29 females.
[0768] 2. Method of treatment. DSP was given to the Treatment
group, 10 tablets/medication, 3 times/day orally. Di'ao Xinxuekang
Jiaonang was given to the Control group (made by the pharmaceutical
factory of Chengdu Bio-tech Research Institute, Chinese Science
Institute), 200 mg/medication, 3 times/day orally. Both medications
lasted 2-6 months.
[0769] Results
[0770] (1) Symptoms of both groups. There was significant
improvement in palpitation, sense of suffocation, and difficulty
breathing in both groups after treatment. The total clinical
efficiencies of the treatment group and the control were 93% and
73%, respectively, as shown in Table 2-3.
79TABLE 2-3 Comparison of efficacy for symptems in two groups Group
n Efficacy Efficacy Failure Total Efficacy (%) Treatment 60 25 31 4
93.0 Control 60 17 27 16 73.0 Notes: Comparison of the two
treatments, P < 0.01
[0771] (2) ECG treatment of two groups. There were no significant
differences in the heart rhythm of the two groups after treatment.
ST-T and T wave, premature atrial beats, and premature ventricular
beats were improved, but the treatment group showed much more
improvement than the control group, as shown in Table 2-4.
80TABLE 2-4 Comparison of ECG results between the two groups Group
n Efficacy Efficacy Failure Total Efficacy (%) Treatment 60 24 32 4
93.0 Control 60 15 24 11 65.0 Notes: Comparison of the 2
treatments, P < 0.01
[0772] (3) Change in heart ultrasound in two groups. The ultrasound
showed that the change in heart size was not significant before and
after treatment. The pumping power of the left ventricle in
patients in the treatment group increased from 48% to 62%, on
average, after treatment. The contraction percentage of the left
ventricular wall decreased from 46% to 18%, which was better than
the control group, as shown in Table 2-5.
81TABLE 2-5 Comparison of the change in heart ultrasound in
patients in two groups before and after treatment Treatment group
Control group Before After Before After treatment treatment
treatment treatment Enlargement of 18 12 12 1 heart/cases Pumping
power of 48 62 49 52 left ventricle (%) Abnormal 46 18 43 28
Contraction of left ventricul wall (%) Notes: Comparison of two
treatments, P > 0.05
[0773] (4) Testing of normal blood count and liver and kidney
functions:
[0774] No significant differences were found in the two groups
before and after treatment.
[0775] DSP and Di'ao Xinxuekang can both improve cardiac arrhythmia
caused by myocarditis and heart malfunction, but DSP does a better
job than Di'ao Xinxuekang. DSP can improve blood flow to the
cardiac muscles, section ST and T wave in ECGs. In addition, DSP
can also reduce platelet aggregation, and platelet viscosity. The
results show that patients who take DSP in the long term enjoy
relief from symptoms and low reoccurrence of myocarditis.
[0776] 3. Reverse Function of DSP on Left Ventricular Hypertrophy
(LVH)
[0777] This experiment explored the reverse function of DSP on
LVH.
[0778] 1. Subject and Method
[0779] 1.1 Sample selection. All patients were selected from
clinics and hospitals and do not have high blood pressure, coronary
heart disease, myocardial disease, diabetes, or other heart
diseases. LVH was confirmed by ultrasonic ECG. The patients were
divided into two groups at random: 34 patients in the treatment
group, including 21 males and 13 females; 20 patients in the
control group, including 12 males and 8 females. There was no
difference in age, sex, and medication in the two groups.
[0780] 1.2 Method. DSP was given to the treatment group, 10
tablets/medication, 3 times/day. 50 mg Meiduoxin'an was given to
the control group, 3 times/day. Each medication lasted 6-12 months.
Other blood vessel medications were stopped during treatment. For
comparison, the two groups were checked and results logged before
and after treatment.
[0781] 1.3 Types of measurements and standards. The heart
ultrasound was checked by color doppler. The dilated Left
Ventricular Interior Diameter (LVID) was measured. Interventricular
septum thickness (IVST) and Left Ventricular Posterior Wall
Thickness (LVPWT) were measured and calculated: Left Ventricular
Mass (LVM)=1.04.times.[(LVID+LVPWT+IVST).sup- .3-LVID.sup.3]-1.36
and Left Ventricular Mass Index (LVMI)=LVM/Surface Area. LVH
standard: a) IVST.gtoreq.12 mm; b) LVPWT.gtoreq.12 mm; c)
LVMI.gtoreq.135 g/m.sup.2 (male) or 110 g/m.sup.2.
[0782] Results
[0783] 2.1 Effects on LVH retreatment. IVST, LVPWT and LVMI in the
treatment group decreased significantly (P<0.05 or 0.01), though
the above standards also decreased in the control group. There were
no significant treatment effects, as shown in Table 3-1.
82TABLE 3-1 Comparison of LVH index in B-ultrasound in 2 groups
before and after treatment Treatment group Control group Types
Before treatment After treatment Before treatment After treatment
LVID (mm) 5.58 .+-. 0.59 5.21 .+-. 0.33* 5.62 .+-. 0.64 5.59 .+-.
0.65 IVST (mm) 13.6 .+-. 1.3 10.9 .+-. 1.4** 12.8 .+-. 1.6 12.4
.+-. 1.8 LVPWT (mm) 13.0 .+-. 1.7 11.0 .+-. 1.2* 12.6 .+-. 1.5 11.9
.+-. 1.6 LVM (g) 252.6 .+-. 58.2 198.7 .+-. 30.96** 238.6 .+-. 59.8
229.8 .+-. 42.5 LVMI (g/m.sup.2) 136.9 .+-. 22.6 108.9 .+-. 18.6*
139.8 .+-. 19.3 135.7 .+-. 20.6 Notes: *Comparison of results
before treatment, P < 0.05, **Comparison of results before
treatment, P < 0.01
[0784] 2.2 Effects on cardiac function parameters. DSP can increase
SV, CI, VPE, and EWK, and decrease VER, TPR, and HOV. This shows
that it can reduce heart burden and add new functions to the heart,
as shown in Table 3-2.
83TABLE 3-2 Comparison of cardiac function index of two groups
before and after treatment Treatment group Control group Types
Before treatment After treatment Before treatment After treatment
Pulse Volume 68.32 .+-. 1.55 79.87 .+-. 1.92* 70.16 .+-. 1.52 69.68
.+-. 1.20 (SVml/pulse) Heart Index 3.20 .+-. 0.78 3.98 .+-. 0.39*
3.54 .+-. 0.66 3.52 .+-. 0.43 (CL/counts/m.sup.2) Ventricular
1.6210 .+-. 0.16 1.8825 .+-. 0.64** 1.5814 .+-. 0.12 1.6627 .+-.
0.33 Efficient Pumping (VPE kg/Pulse) Ventricular 238 .+-. 1.64 150
.+-. 1.28** 240 .+-. 1.32 238 .+-. 1.56 Ejection- Resistance (VER)
Left Ventricular 0.244 .+-. 0.084 0.297 .+-. 0.021** 0.254 .+-.
0.112 0.271 .+-. 0.03 Cardiac Energy Efficacy (EWK) Peri-Resistance
984.78 .+-. 86.01 902.35 .+-. 54.16** 1103.66 .+-. 74.26 986.58
.+-. 78.27 (TPR dyne sec.sup.2/m.sup.2) Heart oxygen 44.954 .+-.
1.5 41.210 .+-. 1.2* 43.167 .+-. 1.1 42.164 .+-. 0.9 consumption
volume (HOV) Notes: *Comparison of results before treatment, P <
0.05, **Comparison of result before treatment, P < 0.01
[0785] 2.3 Effects on blood pressure and heart rhythm. DSP can
decrease heartbeat, average arterial pressure and RPP, and so
eliminate the triggering factors of LVH, as shown in Table 3-3.
84TABLE 3-3 Changes in heart rate and blood pressure in the two
groups before and after treatment Treatment group Control group
Before After Before After Types treatment treatment treatment
treatment Heart rete 80.2 .+-. 12.18 72.8 .+-. 8.64** 81.00 .+-.
10.20 75.81 .+-. 8.13* Average 118.0 .+-. 9.11 101.11 .+-. 5.50**
116.28 .+-. 10.21 112.92 .+-. 5.8 arterial pressure RPP 116.42 .+-.
13.57 98.46 .+-. 11.29** 118.55 .+-. 12.88 108.86 .+-. 10.64 Notes:
*Comparison of results before treatment, P < 0.05, **Comparison
of results before treatment, P < 0.01
[0786] 2.4 Effects on parameters of blood viscosity. DSP can
decrease blood viscosity, prevent platelet aggregation and blood
vessel resistance, and eliminate the triggering factors of LVH, as
shown in Table 3-4.
85TABLE 3-4 Changes in blood viscosity of the two groups before and
after treatment Treatment group Control group Before After Before
After Types treatment treatment treatment treatment Blood 4.714
.+-. 0.34 3.680 .+-. 0.12** 4.773 .+-. 0.36 4.631 .+-. 0.24
viscosity (.eta.b) Blood .sup. 7.889 .+-. 6.326 .+-. 0.14** 7.416
.+-. 0.12 7.385 .+-. 0.18 reduction 0.030 (.eta.r) Plasma 2.532
.+-. 0.13 1.400 .+-. 0.08* 2.486 .+-. 0.16 2.495 .+-. 0.12
viscosity (.eta.p) Notes: *Comparison of results before treatment,
P < 0.05, **Comparison of results before treatment, P <
0.01
[0787] 2.5 Effects on standards of atherosclerosis. DSP increases
APOA-1 (Apoprotein A), SOD, and APOB.sup.-100 and decreases WsFs,
which can prevent atherosclerosis and bring about anti-aging
functions, as shown in Table 3-5.
86TABLE 3-5 Comparison of indexes of atherosclerosis in two groups
before and after treatment Treatment group Control group Before
After Before After Types treatment treatment treatment treatment
APOA.sup.-1 108.9 .+-. 46.8 134.3 .+-. 50.6** 122.4 .+-. 48.4 130.6
.+-. 46.9 (mg/ml) APOB.sup.-100 161.2 .+-. 62.6 120.8 .+-. 52.4*
153.4 .+-. 66.2 148.9 .+-. 53.8 (mg/ml) WsFs (u) 17.8 .+-. 7.9 13.5
.+-. 2.4** 16.9 .+-. 8.6 15.8 .+-. 2.2 SOD (u/ml) 272.86 .+-.
110.30 361.87 .+-. 92.44** 286.31 .+-. 99.71 302.13 .+-. 96.25
Notes: *Comparison of results before treatment, P < 0.05,
**Comparison of result before treatment, P < 0.01
[0788] 2.6 Effects on nail bed microcirculation. DSP can
significantly improve the blood circulation and blood flow and
increase the oxygen-carrying capacity of red blood cells, as shown
in Table 3-6.
87TABLE 3-6 Comparison of the nail bed micro-circulation standard
in two groups before and after treatment Treatment group Control
group Before After Before After Types treatment treatment treatment
treatment Flow speed (mm/s) 0.126 .+-. 0.413 0.332 .+-. 0.111*
0.125 .+-. 0.430 0.185 .+-. 0.419 Blood vessel 64.21 .+-. 37.32
63.92 .+-. 37.66 63.86 .+-. 31.85 62.88 .+-. 34.22 heterozygosity
(%) Fluid cloudiness 28 82.4% 5 14.8%** 18 52.9% 15 44.1%
Dotted-line state 6 17.6% 29 85.2%** 16 47.1% 19 55.9% Notes:
*Comparison of results before treatment, P < 0.05, **Comparison
of results before treatment, P < 0.01
[0789] Discussion
[0790] The above experiment shows that DSP prevents damage caused
by free radicals, prevents atherosclerosis, improves blood
circulation, decreases blood viscosity and exterior blood vessel
resistance, and regulates compliance of cardiac muscles to reverse
LVH.
[0791] 4. DSP Treatment for High Blood Pressure
[0792] (1) Effects on Structure and Functions of Heart in Patients
with High Blood Pressure and Coronary Heart Disease
[0793] 1. Subject. 140 patients with high blood pressure and
coronary heart disease for 4-15 years were selected. The ratio of
males to females is 5:1.
[0794] 2. Method. No angina- and blood pressure-lowering
medications were taken 1 week before treatment. A placebo was taken
3 times/day for 1 week, followed by 10 DSP tablets, 3 times/day.
Each medication was taken for 8 weeks.
[0795] 3. Standards. Static ECG, blood pressure, heartbeat,
clinical symptoms and other undesirable responses; the levels of:
Epinephrine (E), Non-Epinephrine (NE), Atrial Natriuretic Factor
(ANF), endothelins (ET), Nitrogen Monoxide (NO); the structure and
functions of the Left Ventricle (Left Ventricular Dilated diameter,
LVDd, Interventricular space, IVS, left ventricular posterior wall,
PWT, and Left Ventricular Mass Index LVMI).
[0796] 4. Standards of measurement. The structure and function of
the left ventricle was measured by colored ultrasonic doppler, and
the LDVd, IVS and PWT were found. LVMI was calculated according to
the equation: LVMI={1.04 [LDVd+IVS+PWT].sup.3-13.6} 2/surface area,
male >125 g/m.sup.2, female>110 g/m.sup.2 are regarded as
LVH. According to the Teichholz equation and the frequency of blood
flow in the aorta, cardiac output (CO) and ejection fraction (EF)
were calculated, and A peak velocity (DAV), E peak velocity (DEV)
and A/E ratio were measured according to the greatest blood flow
through the biscupid valve. The above results were taken from the
average value of 3 trials.
[0797] 5. Statistics: Results are in terms of X.+-.s. Using
matching t statistic testing before and after treatment.
[0798] Results
[0799] (1) Symptoms of angina and ECG treatment (See Table
4-1):
88TABLE 4-1 Obvious Total Sample Efficacy Efficacy Failure Efficacy
Types Number (%) (%) (%) (%) Symptoms 140 48 80 12 91.4 of Angina
ECG 100 40 32 28 80 section ST
[0800] (2) Change in blood pressure and heartbeat. Heartbeat slowed
to 76.24.+-.9.37 counts/min (P<0.01). Systolic pressure (SBP)
dropped from 20.9+1.71 Kpa to 19.40.+-.1.74 Kpa, diastolic pressure
(DBP) dropped from 12.07.+-.1.99 Kpa to 10.69.+-.0.70 Kpa.
[0801] (3) Change in ANP, ET, NO, NE, E before and after treatment
(See Table 4-2): DSP can lower ET, ANP, NE, E but raises NO.
89TABLE 4-2 AUP (pg/L) ET (pg/L) NO (mol/L) NE (pg/L) E (pg/L)
Before 132.7 .+-. 3.84 48.9 .+-. 11.8 10.97 .+-. 4.3 0.43 .+-. 0.02
0.098 .+-. 0.02 treat- ment After 93.8 .+-. 27.5** 29.4 .+-. 0.6*
16.7 .+-. 8.6* 0.2 .+-. 0.03* 0.07 .+-. 0.01* treat- ment Notes:
Comparison before and after treatment, *P < 0.05, **P <
0.01
[0802] (4) Effects on structure of left ventricle (See Table 4-3.)
DSP can lower IVS, PWT and LVMI.
90TABLE 4-3 LVDd (mm) IVS (mm) PWT (mm) LVMI (g/m.sup.2) Before
treatment 46.9 .+-. 2.67 12.83 .+-. 2.48 11.93 .+-. 1.51 132.89
.+-. 28.66 After treatment 40.2 .+-. 3.09* 9.82 .+-. 1.44** 8.28
.+-. 1.36* 121.58 .+-. 26.84** Notes: Comparison before and after
treatment, *P < 0.05, **P < 0.01
[0803] (5) Effects on functions of left ventricle (See Table 4-4).
DSP can obviously improve diastolic function of the left
ventricle.
91TABLE 4-4 EF (%) DAV (m/s) DEV (m/s) A/E Before treatment 50.14
.+-. 11.02 0.75 .+-. 0.13 0.73 .+-. 0.19 1.21 .+-. 0.32 After
treatment 51.47 .+-. 9.81 0.57 .+-. 0.41* 0.89 .+-. 0.12* 0.98 .+-.
0.34** Notes: Comparison before and after treatment, *P < 0.05,
**p < 0.01
[0804] (6) Undesirable responses: No undesirable responses were
observed in these group.
[0805] Discussion
[0806] The experiment shows that DSP can stop and improve LVH and
dilate the left ventricle, which can then lower blood pressure and
combat angina.
[0807] (2) Effects on Plasma ET and Anti-Insulin Function with
Hypertension
[0808] 1. Aims. Examine the effects of DSP on plasma ET and
anti-insulin function in patients with hypertension.
[0809] 2. Subject. 80 patients with satisfactory results after 1
week of treatment with Amlodipine were selected.
[0810] 3. Method. The 80 patients were divided into 2 groups: the
Control group, with normal treatment, and the DSP group, with 10
DSP tablets, 3 times/day. Testing lasted 4 weeks. 4. Results. (1)
Change in plasma ET and blood pressure before and after treatment
(See Table 4-5.). After treatment, plasma ET in both group was
lower, (P<0.05), especially that of the DSP group
(P<0.05).
92TABLE 4-5 Comparison of related data between the Amlodipine group
and the Amlodipine plus DSP group before and after treatment
Amlodipine plus DSP Amlodipine group group (n = 40) (n = 40)
Relative Before After Before After data treatment treatment
treatment treatment Weight 23.39 .+-. 1.82 23.37 .+-. 1.67 23.95
.+-. 2.01 23.96 .+-. 1.92 Index (kg/m.sup.2) SBP (kPa) 21.43 .+-.
1.69 17.39 .+-. 1.44 21.40 .+-. 1.67 18.09 .+-. 1.55 DBF (kPa)
12.72 .+-. 0.58 11.01 .+-. 0.59 12.85 .+-. 0.54 11.25 .+-. 0.68
Plasma ET 56.4 .+-. 6.78 38.7 .+-. 4.62 57.2 .+-. 7.31 42.6 .+-.
4.78 (ng/L)
[0811] (2) Comparison of insulin level and insulin reactivity
before and after treatment (See Table 4-6). There was no
significant difference in the weight index of the two groups both
before and after treatment. After 4 weeks of treatment, the insulin
level in the DSP group was lower than before (P<0.05).
Insulin/blood glucose ratio was also lower than before treatment.
However, there was no difference in insulin level and insulin/blood
glucose ratio in the control group both before and after
treatment.
93TABLE 4-6 Comparison of related parameters in the
hypertension-with-pure-amino-chloride-horizons group and the DSP
group before and after treatment Amlodipine plus DSP group (n = 40)
Amlodipine group (n = 40) Relative Before After Before After data
treatment treatment treatment treatment Blood glucose (mmol) Empty
5.26 .+-. 0.84 5.01 .+-. 0.78 5.19 .+-. 0.56 5.27 .+-. 0.59 60 min
9.63 .+-. 1.94 7.26 .+-. 0.31 9.86 .+-. 0.65 9.76 .+-. 0.52 120 min
7.64 .+-. 0.80 6.21 .+-. 0.15 7.69 .+-. 0.81 8.01 .+-. 0.76 Blood
insulin (mU/L) Empty 26.24 .+-. 1.83 20.32 .+-. 1.57 25.34 .+-.
1.74 25.31 .+-. 1.73 60 min 126.79 .+-. 1.90 99.66 .+-. 2.00 122.01
.+-. 1.91 121.65 .+-. 1.89 120 min 90.53 .+-. 1.75 71.42 .+-. 1.96
91.62 .+-. 1.96 92.56 .+-. 1.66 Insulin/ 5.06 .+-. 1.29 4.19 .+-.
0.93 5.24 .+-. 1.01 5.18 .+-. 1.07 blood glucose ratio
[0812] Conclusion
[0813] Besides controlling blood pressure efficiently, other
important steps for treating high blood pressure include:
increasing the reactivity of insulin, lowering insulin level, and
improving ET function in blood vessels. DSP is helpful because it
also lowers blood pressure.
[0814] 3. Treatment of Hyperlipidemia
[0815] (1) Treatment of Hyperlipidema
[0816] Research into the treatment of hyperlipidemia and
atherosclerosis with DSP in comparison to low-dosage aspirin.
[0817] 1. Subject and Method
[0818] 1.1 Sample. 53 patients were divided into 2 groups, at
random: 25 patients in Treatment group (DSP group), and 28 patients
in Control group (aspirin group).
[0819] 1.2 Method: DSP was given to the treatment group, 10
tablets/day, 3 times/day. The medication lasted for 6 months. 50 mg
enteric aspirin was given to the Control group, 1 time/day
orally.
[0820] 1.3 Standard. a) Measurement of IMT (Arterial tunica
intima-tunica media). The horizontal and vertical transactions of
the whole-length aorta, carotis communis, exterior artery, and
subclavial artery were checked 1, 2, 3, and 6 months after
treatment. The thickest part of the IMT was measured and recorded.
b) Blood flow included whole blood high-viscosity (hHb), whole
blood low-viscosity (hLb), plasma viscosity (hP), Aggregation Index
of Red blood cells (AIR) etc. c) Measurement of blood lipoprotein
included Total blood Cholesterol (TC) and Triglycerides (TG). D)
Statistical treatment by matching t statistic testing.
[0821] Results
[0822] (1) The medication lasted for 6 months, and the results of
the IMT test are shown in Table 5-1. The carotis communis becames
thinner in the Treatment group (P<0.05), but there was no
observable change in that of the control group.
94TABLE 5-1 Measurement of Arterial IMT in 2 groups after treatment
Group Sample number IMT (mm) DSP Before treatment 41 2.2 .+-. 0.7
After treatment 41 2.1 .+-. 0.6* Aspirin Before treatment 43 2.0
.+-. 0.8 After treatment 43 2.1 .+-. 0.7 Notes: Comparison of
results before treatment in the same group, *P < 0.05
[0823] (2) Blood flow results are shown in Table 5-2. Blood
viscosities in the two groups decreased after 6 months on
medication, and there were no significant differences in the level
of decrease, (P>0.05).
95TABLE 5-2 Results of blood flow in two groups of patients before
and after treatment Sample .eta. .eta. .eta. Group Number Hb (mpa
.multidot. s) Lb (mpa .multidot. s) P (mpa .multidot. s) AIR DSP
Before 25 6.23 .+-. 1.67 10.92 .+-. 2.21 1.95 .+-. 0.08 1.79 .+-.
0.13 treatment After 25 4.35 .+-. 1.02* 8.30 .+-. 1.14* 1.77 .+-.
0.08* 1.39 .+-. 0.11* treatment Aspirin Before 28 6.12 .+-. 1.56
10.38 .+-. 1.96 1.89 .+-. 0.12 1.82 .+-. 0.17 treatment After 28
4.28 .+-. 1.07* 8.21 .+-. 1.03* 1.67 .+-. 0.07* 1.40 .+-. 0.10*
treatment Notes: Comparison of results before treatment in the same
group, *P < 0 .01
[0824] (3) Results of blood lipoprotein testing are shown in Table
5-3, TC and TC level decrease significantly in DSP group after 6
months of medication (P<0.01), and there is no observable
difference in the control group.
96TABLE 5-3 Results of blood lipoprotein testing before and after
treatment in the two groups Sample Group Number .eta.Hb (mpa
.multidot. s) .eta.P (mpa .multidot. s) DSP Before treatment 41
6.08 .+-. 1.5 1.91 .+-. 0.68 After treatment 41 4.91 .+-. 1.44*
1.54 .+-. 0.56* Aspirin Before treatment 43 6.10 .+-. 1.67 1.83
.+-. 0.82 After treatment 43 5.92 .+-. 1.81 1.76 .+-. 0.94 Notes:
Comparison of results before treatment in the same group, *P <
0.01
[0825] Discussion
[0826] This research shows that DSP can significantly lower blood
lipoprotein level and improve blood flow, especially by the
thinning of IMT after treatment. It explains how this drug can
prevent atherosclerosis besides providing the above functions.
[0827] (2) Observation of treatment of senior group coronary heart
disease, angina with high blood viscosity
[0828] 1. Sample. 48 patients with angina and high blood viscosity
were selected, including 39 males and 9 females; 41 patients had
stable angina, and 7 patients had unstable angina.
[0829] 2. Method of medication. All other medications were stopped
2 weeks before DSP administration. DSP was given under lingua, 10
tablets/medication, 3 times/day. The medication lasted 4 weeks.
Blood was collected though the superior venous cava the morning
before ingestion to test blood flow standards and observe angina
conditions and side effects after treatment.
[0830] Results
[0831] (1) Angina improvement. 25 patients were regarded as obvious
efficacy (52.0%), 16 were efficacy (33.3%), 7 were failures
(14.5%).
[0832] (2) Changes in blood flow standards are shown in Table
5-4.
97TABLE 5-4 Change in blood flow standards Before After P Types
treatment treatment value Whole high blood-viscosity 6.76 .+-. 3.22
4.53 .+-. 1.06 <0.01 value Whole high blood viscosity 9.93 .+-.
3.42 7.81 .+-. 1.83 <0.01 value Plasma viscosity 1.91 .+-. 0.18
1.70 .+-. 0.16 <0.05 Erythrocyte hematocrit 0.44 .+-. 0.08 0.43
.+-. 0.07 >0.05
[0833] (3) Observation. 1 out of 48 patients showed serious side
effects, but no bleeding or headache. 3 patients suffered from
stomachaches after the third day of medication. Symptoms
disappeared if the medication was taken after meals. 1 patient
suffered from a swollen head. The symptoms disappeared after
continuous treatment.
[0834] Conclusion
[0835] DSP is safe and effective for senior patients with coronary
heart disease with angina and high blood viscosity.
[0836] 6. Treatment for Hyperviscosity Syndrome (HS)
[0837] Hyperviscosity Syndrome (HS) is a pathobiological concept, a
syndrome caused by one or more blood viscosity factor(s). It can
lead to lack of blood supply, hypoxia, blocking, etc. in the heart,
brain and kidneys. DSP offers the best results in HS treatment.
[0838] There were 41 patients in this experiment, including 23
males and 18 females, aged 39-68. The average age was 50.7. The
primary disease in this group was II-phase hypertentive disease. 22
patients had hypertentive disease and hypertentive nephrosis, 9 had
cerebral infraction, 13 had coronary heart disease; 19 patients had
nephrotic syndrome. DSP was given, 10 tablets/medication, 3
times/day and the medication lasted for 4 weeks. t statistic
testing was used for comparison before and after treatment.
[0839] Results
[0840] After the normal 28 days of medication, HS symptoms such as
nausea, lack of energy, breath holding, anxiety, etc. related to
coronary heart disease, cerebral infraction, and kidney disease
disappeared gradually. Blood pressure was lowered, and blood
circulation improved. TC, TG, Apo-B dropped, and HDLC and Apo-A1
rose. All levels of hemorheology markers dropped. Renal Blood flow
increased, and renal function improved. Urine protein decreased,
and cardiac improved. See Tables 6-1, 6-2, 6-3.
98TABLE 6-1 Change in blood lipoproteins and apoproteins before and
after HS (x .+-. s) TC TG HDLC Apo-A1 Apo-B (mmol/L) (mmol/L)
(mmol/L) (g/L) (g/L) Before treatment 8.07 .+-. 1.45 2.41 .+-. 1.32
1.21 .+-. 0.29 1.27 .+-. 0.18 1.58 .+-. 0.46 After treatment 6.26
.+-. 1.53 2.03 .+-. 1.46 1.37 .+-. 0.31 1.48 .+-. 0.19 1.06 .+-.
0.45 P value <0.01 <0.01 <0.01 <0.01 <0.01
[0841]
99TABLE 6-2 Change in blood flow before and after HS (x .+-. s)
Before Types treatment After treatment P value Whole blood 7.94
.+-. 1.28 5.06 .+-. 1.19 <0.01 viscosity (high-density) Whole
blood 11.87 .+-. 1.69 8.07 .+-. 1.25 <0.01 viscosity
(low-density) Plasma 1.96 .+-. 0.37 1.48 .+-. 0.16 <0.01
viscosity Hematocrit 46.85 .+-. 3.11 42.79 .+-. 3.15 <0.01
Aggregation 2.08 .+-. 0.14 1.39 .+-. 0.13 <0.01 index of red
blood cells
[0842]
100TABLE 6-3 Change in blood pressure, heart rate and cardiac
function before and after HS Heartbeat Cardiac SBP(kPa) DBP(kPa)
(times/min) functions E/A Before 22.8 1.6 14.9 1.5 81.2 7.5 <1
treatment After 15.9 1.4 11.2 1.3 73.9 6.4 >1 treatment P value
<0.01 <0.01 <0.01
[0843] 7. Treatment for Acute Myocardial Infarction (AMI)
[0844] Effects on Blood Serum Troponin in Patients with AMI
[0845] 1. Subject. 56 patients with AMI, including 34 males and 22
females, aged 40-70 were selected. Patients were divided in a 1:1
ratio into two groups: 28 patients each in the treatment group and
the control group. The Control group consisted of 40 healthy people
tested at random, including 23 males and 17 females, aged
42-73.
[0846] 2. Method of medication. Treatment group: DSP was given, 10
tablets, 3 times/day, for 2 weeks; Control group: Western medical
treatment was used (i.e. absolute bed rest, oxygen intake,
maintaining of the stool in a soft and smooth state). The Control
group also took 10 mg Isordil orally, 3 times/d; 75 mg enteric
aspirin, 1 time/d, 12.5 mg Kaibotong, 2 times/d, 5 mg glyceryl
Trinitrate +polarization solution, mild titration, 1 time/d.
[0847] 3. Observation method. 2 ml of blood was collected from the
inferior vena cava of each patient 6 hrs, 12 hrs, 1 day, 3 days, 5
days, 7 days, 9 days, 11 days, and 13 days after patients entered
the hospital. The blood was tested by one-step sandwich enzyme
immunoassay.
[0848] Results
[0849] (1) The blood serum TnT concentration in a normal person
should be evenly distributed, and the normal value should be
0.26+0.14 ug/L. Those with values higher than 0.38 ug/L were
regarded as significantly increased.
[0850] (2) Results of blood serum TnT concentration in both groups
at different onset times are shown in Table 7-1. TnT concentrations
in the two groups were evenly distributed. The serum TnT in the
treatment group rose 3-6 hrs after onset, and reached its peak on
the 47th day, maintained a high level for 9 days, then returned to
normal on the 11th day. Serum TnT concentration in the Control
group rose 4-6 hrs after onset, reached its peak on the 48.sup.th
day, and maintained a high level for 10 days. It returned to normal
on the 12th day.
101TABLE 7-1 Results of serum TnT concentration in the two groups
at different onset times (ng/L) Group No 0 h 6 h 12 h 1 d 3 d 5 d 7
d 9 d 11 d 13 d With 28 0.29 .+-. 0.17 0.58 .+-. 0.21 0.89 .+-.
0.36 3.27 .+-. 0.93 7.65 .+-. 1.36 5.39 .+-. 1.22 2.85 .+-. 0.81
0.48 .+-. 0.27 0.28 .+-. 0.22 .+-. treat- 0.13 0.12 ment Control 28
0.28 .+-. 0.15 0.67 .+-. 0.26 0.95 .+-. 0.35 4.03 .+-. 1.12 9.64
.+-. 1.79 7.13 .+-. 1.42 4.28 .+-. 1.20 1.63 .+-. 0.68 0.39 .+-.
0.25 .+-. group 0.17 0.14
[0851] (3) Analysis of serum TnT results in the Treatment group and
the Control group is shown in Table 7-2. The peak value in the
Treatment group is much lower than that of the Control group
(P<0.01). The duration of TnT elevation and the time required to
return to normal were significantly shorter than those in the
Control group (P<0.05). No significant difference was observed
in the time required to reach the peak in both groups.
102TABLE 7-2 Result analysis of serum TnT in the two groups Time
Time required to required to return to Sample Peak value reach the
Rising time normal Group Number (ug/L) peak(d) (d) value (d)
Treatment 28 8.96 .+-. 1.57 47.21 .+-. 2.18 9.37 .+-. 1.24 10.96
.+-. 1.39 group Control 28 11.02 .+-. 2.13 48.38 .+-. 2.75 10.16
.+-. 1.36 11.87 .+-. 1.48 group
[0852] Conclusion: DSP can improve blood circulation by dilating
coronary arteries, saving cardiac muscle, minimizing the infarction
area, and protecting myocardial cells. Therefore, DSP can protect
cardiac muscles in the early stages of AMI. It is a convenient
medication with no side effects, which is recommended in the
clinical field.
[0853] 8. Effects on Treatment of Cerebral Infarction Treatment of
Cerebral Infarction
[0854] All cases are confirmed by CT brain scan. Patients were
divided into random groups at a 2:1 ratio. The 102 patients in
Group A were given DSP, 10 tablets/medication, once per 6 hrs
through the nose and given additional treatments according to their
level of illness. These additional treatments included dehydrating
agents, anti-infectants, substances to maintain water and
electrolyte balance, acupuncture, moxibustion, chirapsia, etc.)
Group B received the same treatment except DSP. The medication
lasted for 4 weeks in both groups.
[0855] Treatment standards. Marks were given according to the level
of neurologic impairment and according to clinical efficacy
standards.
[0856] Basic recovery. Level of disablement is grade 0
[0857] (1) Obvious efficacy. Functional damage marks were reduced
21 marks or more, and the level of disablement was grade 1-3.
[0858] (2) Efficacy. Functional damage marks were reduced 8-20
marks.
[0859] (3) Failure. Functional damage marks were reduced or less
than 8 marks were given.
[0860] (4) Worsening. 9 or more functional damage marks were
given.
[0861] Results
[0862] 98 patients with a total efficacy of 96.08% were found in
Group A after treatment. 37 patients with a total efficacy of
72.55% were found in Group B after treatment, according to X.sup.2
statistic testing, P<0.001. This shows that the treatment
results for Group A were much better than that of Group B. See
Table 8-1.
103TABLE 8-1 Comparison of results in the two groups (%) Sample
Basic Obvious Worsen Total Group number recovery Efficacy Efficacy
Failure cases Efficacy Group A 102 14 (13.72) 41 (40.20) 43 (42.16)
4 (3.92) 0 (0) 98 (96.08) Group B 51 5 (9.80) 14 (27.45) 18 (35.30)
11 (21.57) 3 (5.88) 37 (72.55) Notes: Total Efficacy tested by
X.sup.2 statistic testing in the two groups, X2 = 18.133, P <
0.001
[0863] The use of DSP to treat low blood supply to the brain,
cerebral infarction and internal bleeding is very efficient.
[0864] 9. Effects on Blood Micro-Circulation
[0865] Patients with coronary heart disease have a disorder of
hemorheology not only in their systemic circulations, but also in
different levels of micro-circulation. Recently, most patients with
coronary heart disease have lower than half the normal renewal rate
by micro-circulation standards. It shows that patients with
coronary heart diseases also get micro-circulation disorders. Nail
wall or bulbar conjunctiva micro-circulation are used as
observation start points for examining total body
micro-circulation.
[0866] (1) Effects on Nail wall micro-circulation. See Table
3-6.
[0867] (2) Effects on bulbar conjunctiva micro-circulation Effects
of DSP on patients with coronary heart disease, bulbar conjunctiva
micro-circulation and thrombo-elasticity chart. The effects of DSP
on patients with coronary heart disease bulbar conjunctiva
micro-circulation and thrombo-elasticity chart by compared with
Suxiao Jiuxin Wan are discussed.
[0868] 1. Sample. 120 patients are selected who have coronary heart
disease and complain primarily of a congested feeling in their
chests, who experience onset coronary heart disease-angina twice or
more per week. They are divided into groups at random: a) 30
patients in the low-dosage DSP group. b) 30 patients in the
medium-dosage DSP group. c) 30 patients in the high-dosage DSP
group. d) 30 patients in the Suxiao Jiuxin Wan control group.
[0869] 2. Method. DSP and Suxiao Jiuxin Wan were taken orally. The
dosages are taken in the following order; 5 tablets/time, 10
tablets/time, 15 tablets/time, 10 tablets/time in the control
group. No other unrelated medications are taken within 2 hrs after
treatment. The bulbar conjunctiva micro-circulation and
thrombo-elasticity charts are checked after 2 hrs, then rechecked
for changes in different standards of bulbar conjunctiva
micro-circulation at 10, 20, 30, 60, 90, 120, and 240 mins post
treatment. Patients are checked for changes in thrombo-elasticity
after 240 mins.
[0870] 3. Standards: (1) testing of bulbar conjunctiva
micro-circulation: Using a multifunctional microscope, the state of
bulbar conjunctiva micro-circulation of the temporal left eye is
magnified 50 times and observed. Sharp blood flow is chosen, blood
capillaries and veins are recorded. The diameter and blood flow
velocity of blood capillaries and veins by the PC processing system
of microcirculation image (MCMP). Blood flow in capillary vessels
is calculated, [blood flow volume=.pi..times.(diameter of blood
vessel/2).sup.2.times.blood flow velocity]. All values used before
treatment in both groups were counted as 100%.
[0871] (2) Testing of thrombo-elasticity. Using the
thrombo-elasticity chart, physical changes in platelet aggregation
and their dissolving process are observed. The main standards were
reaction time(r), aggregation time(k), the maximum amplitude of
thrombo-elasticity chart (ma), and thrombolic cutting-velocity
rate(E)
[0872] Results
[0873] (1) Effects on patients with coronary heart disease bulbar
conjunctiva micro-circulation, see Tables 9-1, 9-2, 9-3, 9-4.
104TABLE 9-1 Effects on diameter of capillary vessels in patients
(M .+-. SD) Low dosage (n = 30) Medium dosage (n = 30) High dosage
(n = 30) Control group (n = 30) Before 100 100 100 100 treatment 10
mins 104.45 .+-. 9.85 131.78 .+-. 9.38 141.27 .+-. 8.45 134.31 .+-.
9.32 after treatment 20 mins 114.36 .+-. 8.76 146.89 .+-. 9.91
156.72 .+-. 9.87 142.71 .+-. 9.65 30 mins 119.32 .+-. 9.34 154.21
.+-. 9.43 178.56 .+-. 9.11* 138.12 .+-. 9.88 60 mins 121.66 .+-.
8.23 156.57 .+-. 8.36* 198.34 .+-. 9.36* 127.85 .+-. 9.13 90 mins
103.26 .+-. 8.89 146.11 .+-. 9.12* 186.46 .+-. 9.89* 110.00 .+-.
9.00 120 mins 109.37 .+-. 8.38 123.45 .+-. 9.21* 143.78 .+-. 9.11*
100.11 .+-. 7.89 240 mins 101.67 .+-. 7.32 119.9 .+-. 6.98 127.72
.+-. 8.11 101.00 .+-. 7.93 Comparison with control group, *P <
0.05
[0874]
105TABLE 9-2 Effects on diameter of capillary vessels in patients
(M .+-. SD) Low dosage (n = 30) Medium dosage (n=30) High dosage (n
= 30) Control group (n = 30) Before 100 100 100 100 treatment 10
mins 99.76 .+-. 5.36 90.31 .+-. 9.11 85.12 .+-. 8.21 88.67 .+-.
5.12 After treatmen 20 mins 9.34 .+-. 8.56 87.34 .+-. 8.87 81.46
.+-. 8.81 86.71 .+-. 7.21 30 mins 96.12 .+-. 9.56 81.35 .+-. 9.11
76.34 .+-. 9.22* 89.56 .+-. 7.33 60 mins 97.66 .+-. 9.21 79.11 .+-.
8.81* 75.74 .+-. 9.12* 91.56 .+-. 9.31 90 mins 99.36 .+-. 8.81
89.37 .+-. 8.85* 83.34 .+-. 7.89* 96.45 .+-. 9.91 120 mins 101.3
.+-. 8.21 95.55 .+-. 9.31 87.36 .+-. 8.21* 97.12 .+-. 7.88 240 mins
104.8 .+-. 7.32 98.91 .+-. 6.56 96.72 .+-. 8.14 98.00 .+-. 7.56
Comparison with control group, *P < 0.05
[0875]
106TABLE 9-3 Effects on blood flow velocity in capillary vessels in
patients (M .+-. SD) Medium Control Low dosage dosage High dosage
group (n = 30) (n = 30) (n = 30) (n = 30) Before 100 100 100 100
treatment 10 mins 104.05 .+-. 5.36 124.31 .+-. 9.12 85.12 .+-. 8.21
130.33 .+-. 8.86 After treatment 20 mins 114.34 .+-. 8.81 136.34
.+-. 8.11 81.46 .+-. 8.81 148.71 .+-. 7.32 30 mins 117.10 .+-. 7.34
148.56 .+-. 8.87 76.34 .+-. 9.22* 139.66 .+-. 8.11 60 mins 121.56
.+-. 6.78 136.13 .+-. 8.56* 75.74 .+-. 9.12* 133.34 .+-. 8.87 90
mins 109.34 .+-. 6.69 129.73 .+-. 8.11* 83.34 .+-. 7.89* 118.21
.+-. 8.56 120 mins 101.34 .+-. 7.67 118.97 .+-. 8.78 87.36 .+-.
8.21* 112.34 .+-. 6.85 240 mins 108.10 .+-. 8.95 110.37 .+-. 7.87
96.72 .+-. 8.14 108.87 .+-. 7.89 Comparison with control group, *P
< 0.05
[0876]
107TABLE 9-4 Effects on blood flow volume in capillary vessels in
patients (M .+-. SD) Low dosage (n = 30) Medium dosage (n = 30)
High dosage (n = 30) Control group (n = 30) Before 100 100 100 100
treatment 10 mins 119.12 .+-. 4.56 126.71 .+-. 8.81 137.67 .+-.
8.81 123.21 .+-. 8.56 After treatment 20 mins 121.56 .+-. 5.11
134.37 .+-. 8.23 145.45 .+-. 8.65 138.17 .+-. 8.38 30 mins 127.15
.+-. 5.59 139.65 .+-. 8.19 159.76 .+-. 8.23* 131.55 .+-. 8.23 60
mins 128.34 .+-. 6.98 136.31 .+-. 8.37* 166.89 .+-. 8.23* 120.11
.+-. 8.17 90 mins 119.12 .+-. 6.67 128.67 .+-. 8.16* 154.21 .+-.
7.98* 120.34 .+-. 8.36 120 mins 101.56 .+-. 7.66 122.79 .+-. 8.31
145.56 .+-. 8.11* 117.32 .+-. 7.56 240 mins 106.12 .+-. 8.32 110.73
.+-. 7.34 125.70 .+-. 8.56 114.12 .+-. 7.13 Comparison with control
group, *P < 0.05
[0877] (2) Effects on the thrombo-elasticity chart in patients with
coronary heart disease. See Table 9-5.
108TABLE 9-5 Effects on different markers before and after
treatment Medium High Control Low dosage dosage dosage group (n =
30) (n = 30) (n = 30) (n = 30) Before r 2.35 .+-. 1.01 2.56 .+-.
0.980 2.54 .+-. 0.897 2.45 .+-. 0.985 treatment 0.897 0.985 k 4.56
.+-. 1.31 4.34 .+-. 1.23 4.17 .+-. 1.45 4.17 .+-. 1.21 ma 76.3 .+-.
19.8 77.5 .+-. 17.3 46.5 .+-. 18.1 75.7 .+-. 19.3 m.di-elect cons.
321.9 .+-. 24.7 344.4 .+-. 20.9 325.5 .+-. 21.8 311.5 .+-. 23.9
After r 3.56 .+-. 1.78 5.98 .+-. 1.71* 7.32 .+-. 1.67* 4.78 .+-.
1.43 treatment k 4.88 .+-. 1.67 6.82 .+-. 1.88* 8.89 .+-. 1.34*
5.67 .+-. 1.46 ma 75.3 .+-. 16.7 67.3 .+-. 19.2* 60.4 .+-. 18.4*
74.5 .+-. 20.3 m.di-elect cons. 304.8 .+-. 19.35 205.8 .+-. 21.4*
154.2 .+-. 22.5* 292.2 .+-. 25.5 Comparison with control group, *P
< 0.05, normal value: r = 4.35 .+-. 1.089; k = 5.030 .+-. 1.528;
ma = 57.46 .+-. 20.33; m.di-elect cons. = 135.09 .+-. 25.519
[0878] Conclusion
[0879] The above experimental results show that DSP can make an
improvement in bulbar conjunctiva micro-circulation and
thrombo-elasticity in patients with coronary heart disease and
angina.
[0880] 10. Effects on Immunity of Red Blood Cells
[0881] Effects on Immunity in Red Blood Cells
[0882] This experiment uses the blood coagulation method of yeasts
sensitized by complement, C3b -causing yeast aggregation testing
and Enzyme-linked Immunosorbent Assay (ELISA), to test the effects
of DSP on the immunosorbent ability of red blood cells, CIC, and
SIL-2R in patients with coronary heart disease.
[0883] 1. Subject. 20 patients with coronary heart disease who
qualify under the WHO Coronary Heart Disease Standard are
selected.
[0884] 2. Method.
[0885] (1) Testing of immunity of red blood cells. Blood is
collected from veins. Coagulation is prevented with Heparin. Blood
is washed with normal saline 3 times and made up to a
1.times.10.sup.8/ml red blood cell suspension. The immunosorbent
ability of red blood cells is tested using the blood coagulation
method of yeasts sensitized by complement.
[0886] (2) Testing of CIC. The blood serum was collected from
patients, and C.sub.3bSYCA method was used to dilute samples to the
following: 1:8, 1:16, 1:32, 1:64, by.
[0887] (3) Testing of solubility of IL-2R. Blood serum was
collected from patients using ELISA.
[0888] Results
[0889] (1) Effects on immunosorbent ability when the degree of
blood clotting is 1:32. After treatment, immunosorbent ability
increases to more than that before treatment (P<0.01). This
shows that DSP can increase the immunosorbent ability of red blood
cells in coronary heart disease, as shown in Table 10-1.
109TABLE 10-1 Effects on immunosorbent ability in patients with
coronary heart disease Sample 1:4 1:8 1:16 1:32.sup..DELTA.
1:64.sup..DELTA. 1:128 Group number (%) (%) (%) (%) (%) (%) With
treatment 20 20 (100) 20 (100) 20 (100) 19 (95) 16 (90) 8 (40)
Control group 20 20 (100) 20 (100) 19 (95) 12 (60) 5 (25) 0 (0)
Notes: .sup..DELTA.p < 0.01
[0890] (2) Effects on blood serum CIC, whent the degree of blood
clotting is 1:32, after treatment. Its CIC positive percentage is
lower than that before treatment (P<0.01). This shows DSP can
remove CIC inside the body, as shown in Table 10-2.
110TABLE 10-2 Effects on circulating immunocomplex in patients with
coronary heart disease Sample 1:8 1:16 1:32.sup..DELTA.
1:64.sup..DELTA. Group number (%) (%) (%) (%) With 20 17 (85) 15
(75) 8 (40) 3 (15) treatment Control 20 20 (100) 17 (85) 15 (75) 12
(60) Notes: .sup..DELTA.P < 0.01
[0891] (3) Effects on SIL-2R in patients with coronary heart
disease. The SIL-2R content is lower than that before treatment
(P<0.01). This shows that DSP can lower SIL-2R level, as shown
in Table 10-3.
111TABLE 10-3 Effects on SIL-2Rin patients with coronary heart
disease Group Sample number Content in sample With treatment 20
76.38 .+-. 72.08 Control group 20 150.69 .+-. 86.58 Notes: P <
0.01
[0892] Conclusion
[0893] The above experiment shows that DSP can lower SIL-2R level,
strengthen the immune system and the immunosorbent ability of red
blood cells.
[0894] 11. Adjustment of Vegetative Nerve
[0895] Adjustment of Vegetative Nerve in patients with Qizhi
Xueyu-type coronary heart disease with angina.
[0896] This test uses "Wenger-Chongzhongchongxiong" vegetative
nerve balance factor analysis to test the heart rate variation
(HRV), that is, the fluctuation in the average heartbeat over, a
certain period of time or over a long time period in the R-R
period. Data, including effects on the sympathetic and
para-sympathetic nerves can be calculated, to reflect the
regulatory function of the vegetative nervous system.
[0897] 1. Sample selection: Patients must have had Qizhi Xueyu-type
coronary heart disease with angina. Patients were divided into two
groups at random. Treatment group: DSP was given, 10
tablets/medication, 3 times/day. Control group: Isordil was given,
10 mg per dosage, 3 times/day. Each medication lasted for 1
month.
[0898] 2. Standard. (1) The Vascular Nerve Balance Index was
recorded before and after treatment as (y): using the
"Wenger-Chongzhongchongxiong- ", vegetative nerve balance factor
analysis. y=0+0.56 is normal. When y>+0.56 is abnormal, it shows
that the function of the sympathetic nerve increases. When
y<-0.56 is abnormal, it shows that the function of the
para-sympathetic-nerve increases.
[0899] (2) Change in heartbeat before and after treatment (HRV). 24
hrs continuous testing is done to check the ECG change. The
standard deviation (SDNN) in the R-R period in 24 hrs is found.
SDNN is used to represent the change in heartbeat.
[0900] Results
[0901] After DSP treatment, the percentage of y>+0.56 dropped
significantly (P<0.05), but the drop in the Isordil group before
and after treatment was not significant, y>+0.56 (P>0.05).
See Table 11-1. After DSP treatment, SDNN in R-R increased
significantly (P<0.01), and there was no significant difference
in the Isordil group before and after treatment (P>0.05). See
Table 11-2. A decrease in HRV means the sympathetic nerve is
excited. It is directly proportional to the symptoms in coronary
heart disease and the possibility of sudden death and irregularity
of heartbeat. DSP can control over-excitement of the
para-sympathetic nerve and regulate the balance in the vegetative
nerve.
112TABLE 11-1 Change in vegetative nerve balance index before and
after treatment (y) y >+ 0.56 y <- 0.56 Sample Before After
Before After Group number treatment treatment treatment treatment
With 30 13 (43.33) 7 (23.33) 3 (10.00) 2 (6.67) treatment Control
23 10 (43.48) 9 (39.13) 3 (13.04) 1 (4.35) group
[0902]
113TABLE 11-2 Change in HRV before and after treatment Sample
SDNN(ms) P Group number Before treatment After treatment value With
30 4.20 .+-. 0.19 4.41 .+-. 0.29 <0.01 treatment Control 23 4.18
.+-. 0.20 4.23 .+-. 0.21 >0.05
[0903] 12. DSP Treatment for Liver Disease
[0904] (1) Research on the Prevention of Chronic Liver Fibrosis
[0905] 1. Clinical Materials.
[0906] 1.1 Normal materials. According to the China Viral Hepatitis
Association Classification Standards of 1990, 45 patients were
confirmed to be infected with chronic active hepatitis, 20 patients
with early-stage liver fibrosis. 55 were male and 10 were
female.
[0907] 1.2 Treatment method. Chronic active hepatitis group:
Qianglining+DSP (group A), Qianglining (group B), Qianglining
injection solution (made by the Jiangsu Tianqing pharmaceutical
company) 80-100 ml/day for 6 weeks. 30 tablets of DSP were taken
each day, for 3 months and 45 tablets of DSP were given to the
early-stage liver fibrosis group each day for 3 months.
[0908] Results
[0909] (1) Improvement of clinical symptoms of chronic active
hepatitis B by Qianglining+DSP treatment (See Table 12-1.).
114TABLE 12-1 Comparison of the improvement in symptoms by combined
treatment and single Qianglining Low Energy Indigestion Swollen
abdomen Liver discomfort Group A Group B Group A Group B Group A
Group B Group A Group B Difference 45 45 43 44 38 36 32 30 before
treatment Recovery 41 34 39 37 36 27 29 25 after (91.1) (75.6)
(90.7) (84.1) (94.7) (75.0) (90.6) (83.3) treatment (%) P value
<0.05 >0.05 <0.05 >0.05 Mean 13.6 .+-. 2.4 19.1 .+-.
2.9 15.8 .+-. 2.6 17.8 .+-. 2.5 10.8 .+-. 1.9 17.4 .+-. 2.8 15.2
.+-. 2.3 16.8 .+-. 2.5 recovery day (Mean .+-. SD) P value <0.05
>0.05 <0.05 >0.05
[0910] As shown in Table 12-1: Qianglining+DSP can improve low
energy situations, swollen abdomen, and other symptoms, which is
different from the recovery percentage and recovery time in the
control group (P<0.05).
[0911] (2) Chronic active hepatitis B recovery After
Qianglining+DSP treatment (See Table 12-2.).
115TABLE 12-2 Recovery of physical signs of two groups after
treatment Size of liver Size of spleen Yellowing of eyes Group A
Group B Group A Group B Group A Group B Abnormal 23 20 15 16 19 18
number before treatment Efficient 25 9 7 1 18 15 number after
(88.5) (45.0) (46.7) (6.3) (94.5) (83.3) treatment (%) P value
>0.05 <0.05 >0.05 Mean 33.6 .+-. 3.8 36.5 .+-. 4.9 58.9
.+-. 9.6 65 18.4 .+-. 3.3 29.6 .+-. 5.1 recovery days (mean .+-.
SD) P value >0.05 >0.05 <0.05
[0912] As shown in Table 12-2, the sizes of livers and spleens
decreased and softened after compound treatment. There was an
obvious difference in the percentage of patients with smaller
spleens and in the recovery time compared with the control group
(P<0. 05). Decoloration was also obvious.
[0913] (3) Liver functions recovery in chronic active hepatitis B
(See Table 12-3.).
116TABLE 12-3 Liver functions recovery in the two groups before and
after treatment ALT AST A/G DBIL Group A Group B Group A Group B
Group A Group B Group A Group B Abnormal 45 45 44 45 25 21 32 29
number before treatment recovery 43 37 41 36 18 14 30 24 number
(95.6) (82.2) (93.2) (80.0) (72.0) (66.7) (93.8) (82.8) after
treatment (%) P value <0.05 <0.05 >0.05 <0.05 Mean 19.1
.+-. 3.4 28.4 .+-. 3.1 22.6 .+-. 4.0 37.8 .+-. 3.9 35.9 .+-. 7.2
39.1 .+-. 7.4 26.5 .+-. 3.2 34.7 .+-. 3.7 recovery number (mean
.+-. SD) P value <0.05 <0.05 >0.05 <0.05
[0914] As shown in Table 12-3, Qianglining+DSP can lower ALT and
the serum bilirubin level and shorten the mean recovery time
(P<0.05) but the change in protein ratio is not significant.
[0915] (4) Effects on liver fibrosis in chronic active hepatitis B
(See Table 12-4.).
117TABLE 12-4 Change in liver fibrosis indexes in the two groups
after treatment Glycocholic acid Hyaluronic acid Procollagen
peptide III Laminin Group A Group B Group A Group B Group A Group B
Group A Group B Mean before treat- 46.5 .+-. 6.2 48.9 .+-. 6.7
246.2 .+-. 20.5 251.8 .+-. 11.4 188.6 .+-. 9.7 169.9 .+-. 9.5 385.7
.+-. 21.1 391.6 .+-. 24.5 ment (mean .+-. SD) Mean after treat-
20.1 .+-. 3.1 42.6 .+-. 5.4 138.9 .+-. 11.4 218.4 .+-. 10.8 89.7
.+-. 7.1 152.4 .+-. 9.2 142.3 .+-. 10.6 298.2 .+-. 16.9 ment (mean
.+-. SD) P value <0.01 <0.05 <0.05 <0.01
[0916] As shown in Table 12-4, liver fibrosis standards drop
significantly after therapeutic alliance (P<0.05).
[0917] (5) Change in early stage liver fibrosis markers (See Table
12-5.).
118TABLE 12-5 Change in early stage liver fibrosis markers III
Glycocholic Hyaluronic Procollagen acid acid peptide Laminin Mean
before 62.8 .+-. 7.4 389.6 .+-. 294.8 .+-. 18.9 517.7 .+-. 24.8
treatment 21.4 (mean .+-. SD) Mean after 37.1 .+-. 62 287.5 .+-.
135.6 .+-. 9.8 282.5 .+-. 10.2 treatment 16.1 (mean .+-. SD) P
value <0.05 >0.05 <0.05 <0.05
[0918] As shown in Table 12-5, DSP can lower levels of liver
fibrosis markers so that the levels of Glycocholic acid,
Procollagen peptide III and Laminin are much lower than those
before treatment (P<0.05).
[0919] (2) 47 Cases of DSP Treatment of Active Liver Fibrosis
[0920] 1. Clinical data. There were 93 cases of active liver
fibrosis caused by viral hepatitis from March 1996 to March 1998.
They were divided into two groups, at random: 47 patients in the
DSP group and 46 patients in the control group.
[0921] 2. Treatment Method. The two groups were given traditional
liver treatments: medical glucose, carnine, conbined energy agent,
vitamin K1, vitamin C, B and human blood products, etc. DSP was
given to the DSP group, 10 tablets/medication, 3 times/day.
[0922] 4. Observation: Hyulronic Acid (HA), III Procollagen peptide
(PIIIP), III Procollagen IV (IV-C), Laminin (LN), .gamma.-spherical
protein, and aminotransferase (ALT).
119TABLE 12-6 Obervable changes PIIIP deviation IV-C deviation HA
deviation B/F A/F B/F A/F B/F A/F treat- treat- treat- treat-
treat- treat- ment ment % ment ment % ment ment % DSP 36 111* 75 38
13* 65.8 36 9** 75 group Ctrl. 34 26 29 37 29 21.6 35 29 17.1 Group
.gamma.-spherical protein LN deviation ALT deviation deviation DSP
41 12* 70.7 47 2.sup..DELTA. 95.7 47 17.sup..DELTA..DELTA. 63.8
group Ctrl. 39 26 33.3 45 7 84.8 45 38 15.6 group Notes: *P <
0.05, *P < 0.01, P > 0.05, .DELTA.P < 0.025.
[0923] Conclusion
[0924] DSP can control clinical liver fibrosis efficiently.
[0925] (3) Treatment of Hepatocirrhosis at the Stage of Losing
Compensation.
[0926] 1. Method. 28 patients with hepatocirrhosis at the stage of
losing compensation, 14 patients were in the Observation group, and
they were given DSP in addition to the ordinary liver protections
and diuretic medications, 15 tablets/each medication, 3 times/day,
for 2 weeks. 14 patients were in the Control group, and the
treatment was the same as the Observation group, without DSP.
[0927] Results
[0928] See Table 12-7.
120TABLE 12-7 Treatment of hepatocirrhosis at the stage of losing
compensation Total Sample Obvious Efficacy Failure Efficacy Group
number Efficacy (%) (%) (%) (%) Observation 14 7 (50.00) 6 (44.29)
1 (7.14) 13 (94.29) group Control 14 3 (21.43) 5 (35.72) 6 (44.29)
8 (57.15) group Notes: Statistically calculated, P < 0.05, there
is a significant difference.
[0929] Conclusion
[0930] There is significant improvement in the treatment of
hepatocirrhosis at the stage of losing compensation when DSP is
added as a medication. DSP does not have side effects and is
helpful--hepatocirrhosis at the stage of losing compensation for
treating hepatocirrhosis at the stage of losing compensation.
[0931] 13. The Effectiveness of DSP Therapy in Diabetes and Related
Complications
[0932] (I) DSP Therapy Improves Diabetic Disease in the Elderly
[0933] 40 diabetic patients were included in the clinical trial.
Their diagnoses met with the diabetic diagnosis standard setup by
WHO in 1985. 21 of the patients were male, aged 70.2+8.4; 19 of
them were female, aged 66.8+5.6. All had suffered from diabetes for
3-25 years with an average of 16.8+6.4. 25 patients also suffered
from cardiovascular disease, 18 had cerebrovascular disease, 8 had
nephrosis, 12 had neuropathy, 15 had eye disease, and 6 had other
complications.
[0934] Patients took DSP orally, twice per day, 10 tablets each
time for 3 months. During the trial, their physical conditions were
monitored by colligation monitoring meter for nail wall
microcirculation, produced by Shanghai Laser Research Center.
[0935] The trial result reveal that after 3 months of taking DSP,
the 40 patients' nail wall microcirculation test indexes had
varying degrees of improvement. Their collective cumulative values
decreased. Among the patients, those originally with serious
abnormalities now had medium abnormality; those originally with
medium abnormality had slight abnormalities. The differences before
and after treatment were obvious. The differences are listed in the
Tables 13-1 and 13-2:
121TABLE 13-1 Changes in nail bed microcirculation before and after
treatment (x .+-. s) Before After Treatment Treatment Tube ansiform
number 3.8 .+-. 1.2 5.2 .+-. 2.8* (strip/mm) Input tube branch ID
7.2 .+-. 2.4 8.0 .+-. 1.6* (.mu.m) Output tube branch ID 8.9 .+-.
3.2 10.1 .+-. 2.7** (.mu.m) loop top ID (.mu.m) 10.8 .+-. 3.6 12.0
.+-. 3.3 Tube ansiform length 389 .+-. 127 360 .+-. 89* (.mu.m)
Crossing number of 52.7 .+-. 19.5 42.8 .+-. 18.2*** tube ansiform
(%) Abnormality number 22.4 .+-. 8.3 19.2 .+-. 7.5** of tube
ansiform (%) Blood vessel 3.0 .+-. 1.5 2.6 .+-. 1.0* motility
(movement tnumber per min) Number of WBC 16.4 .+-. 8.6 14.0 .+-.
7.4* (No./15 second) Compared with the Index Before Treatment: *P
< 0.05 **P < 0.01 ***P < 0.001
[0936]
122TABLE 13-1 Nail nail bed microcirculation colligation scores
before and after treatment (x .+-. s) Before After Treatment
Treatment Tube ansiform number 3.8 .+-. 1.2 5.2 .+-. 2.8*
(strip/mm) Input tube branch ID 7.2 .+-. 2.4 8.0 .+-. 1.6* (.mu.m)
Output tube branch ID 8.9 .+-. 3.2 10.1 .+-. 2.7** (.mu.m) loop top
ID (.mu.m) 10.8 .+-. 3.6 12.0 .+-. 3.3 Tube ansiform length 389
.+-. 127 360 .+-. 89* (.mu.m) Crossing number of 52.7 .+-. 19.5
42.8 .+-. 18.2*** tube ansiform (%) Abnormality number 22.4 .+-.
8.3 19.2 .+-. 7.5** of tube ansiform (%) Blood vessel 3.0 .+-. 1.5
2.6 .+-. 1.0* motility (movement tnumber per min) Number of WBC
16.4 .+-. 8.6 14.0 .+-. 7.4* (No./15 second) Compared with the
Index Before Treatment: *P < 0.05 **P < 0.01 ***P <
0.001
[0937] (II) DSP Heals Diabetic Neuritis
[0938] 1. Clinical Information. There were a total 36 patients, 9
of them were male, 27 of them were female. The eldest was 82 years
old; the youngest was 45 years old. The patient with the longest
history of suffering from the disease had it for 4 years prior to
the study. The patients were selected according to the diagnosis
standard on page nine of Diabetic Neuropathy of Practical Internal
Medicine.
[0939] 2. Treatment Method. Controlling blood glucose level in
normal circumstances. 10 tablets of DSP were taken orally after
meals, three times per day. When the disease showed observable
improvement, patients reduced their intake of DSP to 3 tablets, 3
times per day. Each medication lasted 40 days.
[0940] 3. Treatment Results. 31 patients had great improvement
(clinical symptoms disappeared); 5 cases had observable
improvement; none of the cases had no improvement.
[0941] Conclusion
[0942] DSP has positive healing effects on diabetic end-brush
neuritis
[0943] 14. The Effectiveness of DSP Therapy on Optical Fundus
Vascular Diseases
[0944] Healing of Retinal Vein Occlusion by Dan Shen Pill
[0945] 1. Disease Conditions. Among the 42 patients, 27 had the
disease in one eye, 15 had it in both eyes. 18 had central retinal
vein occlussion (CRVO), 24 had branch retinal vein occlussion
(BRVO)
[0946] 2. Treatment Method. (1) Patients orally ingested large
amounts of DSP, i.e. 15 grains each time, 3 times per day. (2)
Patients orally ingested a DSP took injections of urokinase in the
conjunctiva, and orally ingested a suitable dose of hormone. When
patients improved and stablized, they were further treated by
laser.
[0947] 3. Treatment Results: (1) Obviously improved: Patients could
see objects within 5 feet or eyesight becames 1.0 or higher; (2)
Improved: Eyesight improved by 2-4 lines; (3) No change: Eyesight
improved or worsened by 1 line; (4) Worsens: Eyesight worsened by
more than 2 lines. Obviously improved and Improved can be
considered as effective.
[0948] Results
[0949] See Table 15-1.
123TABLE 15-1 Comparison of Eyesight Before and After Treatment
(Unit %) <0.1 0.1-0.5 0.6-1.0 1.0 Before After Before After
Before After Before After BRVO 3 (18) 1 (4) 11 (48) 6 (27) 8 (35)
10 (43) 1 (4) 6 (26) CRVO 10 (58) 9 (47) 8 (42) 8 (42) 1 (5) 2 (11)
0 (0) 0 (0)
[0950] The cause of retinal vein occlusion is still not very clear.
Hypertention, hyperlipidemia, and arteriosclerosis are usually
considered as likely causes of retinal vein occlusion. Doctor of
traditional Chinese medicine believes that it is caused by stagnant
blood flow. DSP can activate blood circulation and relieve
congestion, improve microcirculation, relieve hydropsy, and
encourage blood absorption. In so doing, it can improve eyesight.
DSP can also be used to heal different kinds of optical fundus
vascular diseases that are generally termed as Xueyuzheng, such as
central retinal artery occlusion, hypertensive retinal
arteriosclerosis, diatetic retinal lesion, central plasm optic
neuropathy, central permeation optic neuropathy, ischemic optic
neuropathy, optic neuritis, atrophy of the optic nerve, etc.
[0951] 15. DSP's Effect on Hemorheology
[0952] The effect of DSP on hemorheology of cervical syndrome
patients Patients were selected based on the diagnosis standard set
up during The National Cervical Syndrome Panel Discussion in May
1984. 80 patients were randomly divided into two groups: (1) 50
patients took DSP and Qiankun guzhizengsheng Wan (Observation);
[0953] (2) 30 patients took only Qiankun guzhizengsheng Wan
(Control). The Observation group took 10 grains of DSP 3 times a
day and 1 grain of Qiankun guzhizengsheng Wan twice a day. The
Control group took only 1 grain of Qiankun guzhizengsheng Wan twice
a day. The medication for both groups lasted 2 months.
[0954] Result
[0955] (1) In the Observation group, besides fibrinogen, whole
blood viscosity, whole blood reduction viscosity, plasma viscosity,
hematocrit and Aggregation Index of RBC all decreased. The
differences before and after treatment were obvious (P<0.05 or
P<0.01). Compared with the Control group, whole blood viscosity,
whole blood reduction viscosity, plasma viscosity, Aggregation
Index of RBC had obvious decreases (P<0.05 or P<0.01). After
treatment, the Control group shared an obvious change only in the
hemagglutilation index (P<0.05 or P<0.01). The results are
listed in Table 16-1.
124TABLE 16-1 Changes of hemorheology in the two groups after
treatment (x .+-. s) Whole blood Whole Blood reduction Plasma
Treat- Viscosity viscosity Viscosity Group ment (mPa .multidot. s)
(mPa .multidot. s) (mPa .multidot. s) Observation Before 5.66 .+-.
1.12 8.72 .+-. 1.46 2.16 .+-. 0.82 Group After 4.98 .+-.
0.84.sup..DELTA..DELTA.* 8.01 .+-. 1.25.sup..DELTA.* 1.62 .+-.
0.36.sup..DELTA.** (50 cases) Control Before 5.42 .+-. 1.35 8.72
.+-. 1.52 2.24 .+-. 1.02 group After 5.48 .+-. 1.08 8.74 .+-. 1.43
2.20 .+-. 0.48 (30 cases) Hemagglu- Fibrinogen hematocrit tilation
Group Treatment (g/L) (V) index Observation Before 3.94 .+-. 0.84
48.12 .+-. 3.84 1.08 .+-. 0.14 Group After 3.90 .+-. 0.81 44.70
.+-. 4.67.sup..DELTA..DELTA. 0.86 .+-. 0.12.sup..DELTA..DELTA.**
(50 cases) Control Before 3.98 .+-. 0.90 48.16 .+-. 4.85 1.06 .+-.
0.10 group (30 cases) After 4.02 .+-. 0.87 45.53 .+-. 5.78 0.98
.+-. 0.14.sup..DELTA. Note: Compared with results of pretreatment,
.sup..DELTA.P < 0.05, .sup..DELTA..DELTA.P < 0.01; Compared
with results of post treatment, *P < 0.05, **P < 0.01
[0956] 16. DSP's Healing Effect on Chronic Pulmonary Heart
Disease
[0957] 1. Using DSP to Cure Chronic Pulmonary Heart Disease
[0958] 90 cases of chronic pulmonary heart disease were selected
based on the diagnosis standard set up during the National
Pulmonary Heart Disease Congress in 1977. The patients were divided
randomly into an Observation group and a Control group. The 60
cases in the Observation group took DSP, while the 30 cases in the
Control group took persantin. Based on the objectives of: reduced
inflammation, coughing cessation, dissolving of sputum, cardial and
diuretic action, and cardiac function improvement, the Observation
group was given 10 grains of DSP, 3 times a day. The Control group
was given 50 mg of Poon Seng Ding each time, 3 times a day.
Treatment lasted 1 month.
[0959] 1. Treatment Standard
[0960] (1) Obvious Efficacy. The symptoms such as coughing, asthma,
pulmonary rales, syanosis were relieved or disappeared. The ascites
and lower limbs sdema were disappeared as well. Heartbeat was under
100 times/min and cardiac function was improved above grade I-II.
The urine volume per day increased by 600 ml and above, while the
body weight decreased by 4%. The end-brush circulations were
improved.
[0961] (2) Efficacy. Above all markers were partly improved.
[0962] (3) Inefficacy. Above all markers were not improved.
[0963] 2. Results. Total efficacy rate of treatment group is 95%
and that of control group 76%, the difference of which is
statistically significant (P<0.05=. The result revealed that the
efficacy of DSP is superior to persantin, showed as table 17-1, and
that hemorheology in DSP group has more improvement than that in
persantin group, showed as table 17-2.
125TABLE 17-1 comparison of efficacy rates before treatment and
after treatment Total Case Obvious efficacy Group number efficacy
Efficacy inefficacy rate Treatmeat 60 35 (0.583) 22 (0.367) 3
(0.05) 57 (0.95) group Control 30 14 (0.47) 9 (0.3) 7 (0.23) 23
(0.76) group
[0964]
126TABLE 17-2 Comparison of hemorheologic markers before treatment
and after treatment Treatment group Control group Before After
Before After treat- treat- treat- treat- Group ment ment P value
ment ment P value Blood 4.55 .+-. 0.84 3.54 .+-. 0.63 <0.01 4.35
.+-. 0.81 3.66 .+-. 0.58 <0.05 viscosity Hematocrit 0.53 .+-.
0.05 0.33 .+-. 0.22 <0.01 0.48 .+-. 0.05 0.37 .+-. 0.05 <0.05
(VOL/%) Fibrinogen 4.33 .+-. 0.35 1.073 .+-. 0.145 <0.01 4.22
.+-. 0.34 3.60 .+-. 0.23 <0.05 (g/L) Aggregation 39.27 .+-.
2.137 21.66 .+-. 19.30 <0.01 4.16 .+-. 2.32 32.28 .+-. 20.30
<0.05 rate of platelet (%)
[0965] (2) Treatment of Acute Pulmonary Heart Diseases
[0966] 70 patients with acute pulmonary heart disease were chosen
according to 2nd Whole Nation Pulmonary Heart Disease Conference
Standards, 1977. Both the Treatment and Control were given
treatment designed to reduce inflammation, cease coughing, dissolve
sputum, and act as cardial and diuretics. They were also given
slow-f lowing oxygen. DSP was given on an ordinary treatment basis,
10-15 tablets each, 3 times/day for 2 weeks. 36 patients were in
the control group. All treatments for the control group were the
same as that of the treatment group, except DSP.
[0967] 1. Treatment Standard
[0968] (1) Obvious Efficacy. Pulmonary and cardiac function
improved to grade II, the symptoms such as coughing, expectoration,
dyspnoea, and cyanosis in the resting state were reduced or even
disappeared. The liver becames smaller, and lung rales
disappeared.
[0969] (2) Efficacy. Pulmonary and cardiac function improved to
grade I, and the elimination of clinical symptoms was releaved (3)
Failure. No improvement in or worsening of pulmonary and cardiac
function.
[0970] 2. Results. There was a significant difference in the
efficacy of the two groups (X.sup.2=4.46 and 4.95, P<0.05).
Treatment group results were better than that of the Control group,
as shown in Table 17-3. There were obvious changes in blood flow in
the Treatment group before and after treatment compared with that
of the Control group (P<0.05). The blood viscosity of the
control group decreased after treatment, but there was no
statistical deviation, as shown in Table 17-4.
127TABLE 17-3 Comparison of clinical total efficacy before and
after treatment Sample Obvious Total Group number Efficacy Efficacy
Failure efficacy Treatment 36 17 (0.427) 15 (0.417) 4 (0.111) 32
(0.889) group Control 34 9 (0.265) 14 (0.412) 11 (0.323) 23 (0.677)
group
[0971]
128TABLE 17-4 Blood flow indexes before and after treatment
Treatment group Control group Before After Before After Group
treatment treatment P value treatment treatment P value .eta.b1
(mPa .multidot. s) 9.01 .+-. 1.70 6.11 .+-. 1.13 <0.01 8.98 .+-.
1.82 7.91 .+-. 1.95 >0.05 .eta.bh (mPa .multidot. s) 6.32 .+-.
1.21 5.15 .+-. 0.75 <0.01 6.30 .+-. 1.42 5.91 .+-. 1.77 >0.05
.eta.p (mPa .multidot. s) 1.95 .+-. 0.14 1.70 .+-. 0.08 <0.01
1.92 .+-. 0.12 1.80 .+-. 0.18 >0.05 EAI 1.57 .+-. 0.13 1.40 .+-.
0.08 <0.05 1.60 .+-. 0.15 1.56 .+-. 0.20 >0.05 HCT (%) 46.72
.+-. 5.41 40.69 .+-. 5.16 <0.05 45.93 .+-. 5.32 43.80 .+-. 5.92
>0.05 ET (s) 23.71 .+-. 1.77 20.82 .+-. 1.08 <0.05 24.02 .+-.
1.94 23.34 .+-. 2.06 >0.05 ESR (mm) 24.00 .+-. 11.28 16.60 .+-.
9.30 <0.05 23.89 .+-. 12.02 29.90 .+-. 13.20 >0.05 Fb (mg%)
301.50 .+-. 32.14 270.16 .+-. 20.12 <0.05 299.60 .+-. 39.28
288.10 .+-. 40.36 >0.05
[0972] (3) Treatment of Pulmonary Heart Diseases Causing Red Blood
Cell Proliferation
[0973] 23 patients were chosen according to 2.sup.nd Whole Country
Conference on Lung and Heart Diseases Standards, 1977. Besides the
typical symptoms, hemoglobin content was>160 g/L in males and
>150 g/L in females. Red blood cell pressure was >0.60 in
males and >0.55 in females.
[0974] 10 tablets of DSP were taken 3 times/day. Drugs to fight
infections, cease coughing and asthma, diuresis, dilate vessel, and
glucocorticoid were given during treatment. After 20-56 days of
treatment, (the average was 38 days treatment), there was a
significant improvement in conjunctival congestion and lips,
tongues, and nail bed with cyanosis. Hemoglobin content and
hematocrit also decreased. After treatment (x.+-.s), hemoglobin was
-3.10.+-.2.90, P<0.01, hematocrit was -11.80.+-.2.90, P<0.05,
show a significant difference. There were side effects during
treatment.
[0975] 17. Treatment of Adrenal Syndrome
[0976] Treatment Effects on Nephrotic Syndrome
[0977] 80 patients with nephrotic syndrome were chosen at Wuhan
Hospital from 1998-1999. All the histories, physical signs,
supportive checking, and courses were recorded according to
3.sup.rd Whole Country Kidneys Diseases Association Conference
Standards, 1992. Patients with nephrotic syndromes caused by other
factors were eliminated. Patients were divided into 2 groups, at
random: Control group: Treated with ordinary delta prenovis
treatment and Western medications; Treatment group: DSP, 10-15
tablets, 3 times/day, for 8 weeks; no other cholesterol-lowering,
anti-coagulation, anti-thrombosis, and vessel-dilation drugs with
the ordinary delta prenovis treatment basis.
[0978] 1. Treatment Standards. Classified according to the 2.sup.nd
Whole Country Chinese Medicine Kidney Disease Conference
Standard.
[0979] (1) Complete remission: Symptoms and physical signs
disappeared. Urine protein content was <0.2 g/24 h. Renal
function and blood lipoprotein content become normal. Urine red
blood cell content is exceed 0-3/HP
[0980] (2) Basic remission: Symptoms and physical signs
disappeared. Urine protein content was <1 g/24 h. There was
little Urine red blood cells.about.(+)
[0981] (3) Partial remission: Symptoms and physical signs improved.
Experimental examination standards improved but did not reach basic
retrieval standards.
[0982] (4) Failure: Symptoms and physical sign and experimental
examination results did not change after 2 months on treatment.
[0983] Results
[0984] (1) Table 18-1 shows that the complete reversal percentage
and total efficacy in the treatment group were 55% and 90%,
respectively, which was significantly higher than those in the
control group: 27.5% and 65% (P<0.05). DSP, combined with other
medications, can improve treatment results and reduce the
percentage of reoccurrence.
129TABLE 18-1 Clinical treatment result comparison in 2 groups
Complete Basic Partial Total Cases Retrieval Retrieval Retrieval
Failure Reoccur efficacy Treatment group 40 22 10 4 4 3 90% Ctrl.
group 40 11 9 6 14 8 65%
[0985] (2) Table 18-2 shows that there are no significant
difference in Urine osmotic pressure, Urine lysozime, and Urine C3
testing before and after treatment in the same group (P>0.05),
treatment group and control group after treatment (P>0.05). It
also shows that renal corpuscle and tubule damage is difficult to
recover from in the short run. Table 18-2 shows no significant
abnormality is found in the same group before and after treatment
(P<0.01=and in treatment group and control group after treatment
(P<0.05).
[0986] (3) Table 18-3 shows all different markers before and after
treatment P<0.01. The treatment group and control group
P<0.05 have significant difference, except hematocrit.
130TABLE 18-2 Comparison of parts of biochemical indexes in 2
groups (x .+-. s) Blood Blood Urea Urea Plasma Blood urea immuno-
osmotic protein albumin TG Cholesterol creatinine nitrogen albumin
pressure Urea C3 (g/24 h) (g/l) (mmol/L (mmol/L) (.mu.mmol/L)
(mmol/L) (g/l) (mOsm/kg .multidot. H.sub.2O) Urease (mg/ml) (mg/l)
Treat- B.T 7.10 .+-. 23.30 .+-. 3.79 .+-. 10.83 .+-. 123.7 .+-.
9.95 .+-. 5.39 .+-. 690 .+-. 5.42 .+-. 1.98 .+-. ment 3.67 5.70
1.58 1.23 87.35 3.71 1.70 205 4.23 2.13 group A.T 0.78 .+-. 35.42
.+-. 1.77 .+-. 4.99 .+-. 80.35 .+-. 5.41 .+-. 9.00 .+-. 721 .+-.
5.98 .+-. 1.87 .+-. 0.33 0.76 0.74 0.92 24.67 2.13 2.37 315 4.77
2.27 Control B.T 6.24 .+-. 24.10 .+-. 3.32 .+-. 11.23 .+-. 127.8
.+-. 10.73 .+-. 5.91 .+-. 603 .+-. 6.12 .+-. 2.16 .+-. group 2.35
5.30 1.94 1.35 67.37 4.35 2.48 298 4.15 2.62 A.T 1.76 .+-. 31.47
.+-. 1.99 .+-. 6.82 .+-. 89.74 .+-. 6.90 .+-. 7.87 .+-. 674 .+-.
5.98 .+-. 2.24 .+-. 0.54 2.64 0.92 2.05 51.73 2.21 2.19 213 4.63
2.87 Keys: B.T. = before treatment, A.T. = after treatment
[0987]
131TABLE 18-3 Comparison of blood flow in 2 groups (x .+-. s) Whole
blood Whole blood viscosity viscosity Red blood Aggregation (high
(low- Plasma cell Index of red transect) transect) viscosity
pressure blood cells Treatment Before 7.83 .+-. 1.31 11.78 .+-.
1.96 1.96 .+-. 0.37 46.81 .+-. 3.05 2.09 .+-. 0.11 group treatment
(40 cases) After 4.96 .+-. 1.24 7.91 .+-. 1.52 1.48 .+-. 0.17 42.74
.+-. 3.23 1.41 .+-. 0.21 treatment Control Before 7.46 .+-. 1.19
11.31 .+-. 2.04 1.89 .+-. 0.41 47.01 .+-. 2.99 2.11 .+-. 0.19 group
treatment (40 cases) After 5.47 .+-. 1.35 8.27 .+-. 1.18 1.61 .+-.
0.26 44.35 .+-. 2.72 1.62 .+-. 0.24 treatment
[0988] 8. Treatment of Other Diseases
[0989] (1) Treatment of Bronchitis in Children
[0990] 1. Clinical materials. 78 patients were selected and divided
at random into Treatment group (42 total, 25 males and 17 females),
and control group (36 total, 20 males and 16 females). All patients
stayed in the hospital. The youngest one was 2 months old, and the
oldest one was 12 years old.
[0991] 2. Treatment method. Anti-infectants was given to both
groups, and DSP was given orally to the Treatment group 3 times a
day. Dosage: <1 yr-old, 2 tablets each time; 1.about.3 yr old, 3
tablets each time; 3.about.8 yr-old, 5 tablets each time; 8-12 yrs
old, 8 tablets each time.
[0992] 3. Observation tasks. See Table 19-1.
132TABLE 19-1 Clinical symptoms and experimental results in the two
groups WBC .gtoreq. pneumonia Cough- Lung 10.0 .times. showed by
Group n Fever ing asthma Rales 10.sup.9/L chest X-ray Treat- 42 32
42 10 42 25 42 ment group Control 36 22 36 8 36 20 36 group
[0993] 4. Treatment standards. (1) Obvious efficacy: The child was
free of fever and lung rales after 5 days of treatment. There was
absorption of original lesion focus; (2) Efficacy: Fever and lung
noise mostly disappeared after 5 days of treatment, and there was a
better absorption of original lesion focus after 10 days of
treatment; (3) Failure: No improvements in the above symptoms were
noted, and there was no improvement in the absorption of the
original lesion focus.
[0994] Results
133TABLE 19-2 Treatment of pneumonia in children Average Obvious
Total days of Group Efficacy Efficacy Failure efficacy(%) treatment
Treatment 18 20 4 90.5 10.6 group Control 12 14 10 72.2* 13.4**
group Notes: comparison of 2 groups: *P < 0.05, immediate
significant difference; **P < 0.05, significant difference
[0995] DSP combined with antibiotics can improve treatment results
in infections. The DSP treatment ended fever and rales better than
that of the control group. DSP raised the recovery percentage for
pneumonia in children and shortened the duration of treatment
without significant side effects.
[0996] (2) Effects on hemicrania 58 patients with hemicrania were
selected from clinics. They all qualify under International
Headache Standards classifications. 10 tablets of DSP (25
mg/tablet) were given to the Treatment group, 3 times/day. 5 mg of
Flunarizine was given to the control group, once a day, orally. The
medication lasted 8 weeks. Treatment results and side effects were
recorded every 2 weeks. No other pain-killing medications were
taken within the 6 months.
[0997] Treatment standards. Controlled: Headaches disappeared with
medication, and there was no reoccurrence after treatment ended;
Obvious efficacy: The seriousness of headaches is reduced, duration
is shortened, and onset frequency is reduced to 75% or more;
Efficacy: The level of headache is reduced, and onset frequency is
reduced 50%.about.70%; Failure: No improvement in headaches.
[0998] The result shows that the efficacy in the treatment group is
higher than that of the control group (P<0.05=. DSP can
efficiently cure and prevent hemicrania. See Table 19-3.
134TABLE 19-3 Comparison of DSP and Flunarizine's effects on
hemicrania Obvious Total Controlled Efficacy Efficacy Failure
efficacy DSP group 13 9 5 3 90.00% (30 cases) Flunarizine 5 7 7 9
67.86% (28 cases) Notes: After X.sup.2 statistic testing, P <
0.05
[0999] (3) Treatment of chronic gastritis
[1000] 35 cases of chronic gastritis, including 15 cases of
superficial gastritis, 6 cases of chronic erosive gastritis, and 14
cases of chronic atrophic gastritis were selected. All had blood
congestion, including 3 cases of positive pylora-bacilli positive
and 5 cases of co-duodenal bulb inflammation. 10 tablets of DSP
were taken 3 times a day.
[1001] Treatment standards. (1) Recovery: All symptoms disappeared,
appetite improved, focus inflammation disappeared when observed by
gastroscope; (2) Efficacy: Symptoms mostly disappeared, focus
inflammation showed improvement when observed by gastroscope;
[1002] (3) Improvement: Symptoms were reversed, focus inflammation
showed improvement when observed by gastroscope;
[1003] (4) Failure: No improvement was noted.
[1004] Results
[1005] 12 cases achieved 34.3% recovery; 11 cases achieved 31.4%
efficacy; 8 cases achieved 22.9% improvement; 4 cases failed (11%);
and the total efficacy was 88.7%.
[1006] DSP can regulate the function of blood vessels, restrain
platelet aggregation, control thrombosis, clear out stagnant blood
in the gastric mucosa and cure stamoachache caused by chronic
gastritis. It can efficiently eliminate the dead parts of the
erosive gastric mucinitis, activate megakaryocytes, and stimulate
production of new cells to improve the recovery from
inflammation.
[1007] (4) Treatment of Dizziness
[1008] 61 patients were divided into two groups at random. 29
patients were in the Treatment group, including 22 patients with
insufficient blood supply to the cerebral artery, 7 patients with
Meniere Disease, 5 patients with high blood pressure, and 2
patients with coronary heart disease. 32 patients were in the
control group, including 22 patients with insufficient blood supply
to the cerebral artery, 10 patients with Meniere Disease, 7
patients with high blood pressure, and 4 patients with coronary
heart disease. 10 tablets of DSP were given to the Treatment group,
3-5 times/day for 3-7 days. 50 mg of lidocaine was injected into
the Control group, once a day for 3-7 days.
[1009] Treatment method: (1) Obvious Efficacy: Dizziness and other
companion symptoms disappeared, and there was no re-occurrence for
12 hrs after observation. (2) Efficacy: The level of dizziness and
other symptoms disappeared. (3) Failure: No improvement.
[1010] Results
[1011] The total efficacy in the Treatment group and the Control
group were 86% and 87.5%, respectively. No significant abnormality
was found, as shown in Table 19-4. These two groups of drugs can
treat fainting efficiently. Therefore, DSP can be a convenient and
efficient drug to treat fainting caused by insufficient blood
supply to the brain.
135TABLE 19-4 Comparison of treating dizziness Treatment group
Control group Obvious Total Obvious Total Cases Efficacy Efficacy
Failure efficacy Cases Efficacy Efficacy Failure efficacy Insuf- 23
14 8 1 22 (96%) 22 12 8 2 20 (91%) ficient blood supply to the
brain Meniere 6 0 3 3 3 (50%) 10 6 2 2 8 (80%) disease Total 29 14
11 4 25 (86%) 32 18 10 4 28 (87.5%) Notes: after X.sup.2 statistic
testing, P > 0.05
[1012] (5) Treatment of Damaged Lateral Malleolus Joint
[1013] There were 53 males and 34 females in this experiment, ages
14-60. All cases were selected according to external injury and
typical clinical symptoms after x-ray photography to eliminate
cases of broken bone.
[1014] Treatment method: 30 tablets of ground DSP with 30 ml of 75%
ethanol were mixed to a solution for external use. It was applied
to the injured area 3 times a day with normal medication for 5
days.
[1015] Results
[1016] After DSP treatment, patients felt symptoms disappear and
joint and ligament function recover. There were no obvious pressure
pain spots. 42 patients recovered after 1 treatment, 37 patients
recovered after 2 treatments, and 8 patients recovered after 3
treatements.
[1017] DSP can eliminate swelling and stagnant blood, and can kill
pain. Among their active ingredient borneol can increase its
absorption through the skin and maintain concentrations of the
drugs at the application site, so it can efficiently and quickly
treat damage of the lateral malleolus joint. It is helpful in
treating broken bones, bone death and proliferation of bone.
[1018] (6) Prevention and Treatment of Plateau Hypoxia
[1019] Plateau hypoxia can lead to capillary circulation disorder,
causing blood perfusing insufficiency. Plateau hypoxia also leads
to high blood viscosity, increased red blood cell quantity and red
blood cell aggregation, enhanced red blood cell rigidity, increased
platelet aggregation, and change in pH value. All the above factors
affect blood viscosity and the radius of capillaries. Platelet
aggregation can increase resistance in capillaries, leading to
blockage. When blood viscosity increases, the radius of capillaries
also increases and leads to increased resistance and congestion.
There are common properties in the blood flow of people with
plateau hypoxia: "concentration" (increased red blood cell
pressure), "viscosity" (increased whole blood viscosity),
"aggregation" (increased aggregation of red blood cells). All the
above are different at different sea levels and durations. Fore
mentioned pharmaphysiologic and clinical research show that DSP can
lower hematocrit, blood sedimentation and blood viscosity, so it is
helpful in preventing and treating plateau hypoxia.
[1020] (7) Prevention and Treatment of Senile Dementia
[1021] Senile dementia can be classified as Alzheimer's Disease
(AD), vascular dementia and combined dementia. After DSP treatment,
there is statistically significant improvement in AD and vascular
dementia by measurement analysis and Chinese medicine clinical
observation (p<0.05 or p<0.01). DSP is helpful for treating
sluggishness, reticence, forgetfulness, fatigue, and ecchymosis at
a total efficacy of 40%, and sadness, anger, rashness, and
irritation at a total efficacy of 85.7%.
[1022] Conclusion
[1023] To conclude, DSP can efficiently cure coronary heart disease
in very low dosages. It is well packed, easily absorbed, safe and
has no side effects. It relieves angina efficiently and reduces
onset frequency and level of pain. It can also reduce the volume of
glyceryl trinitrate used. Its total efficacy on angina and ECG
efficacy are higher than that in Isordil in long-term use. It also
improves cardiac function, blood dynamics, ECG, and blood flow in
patients with coronary heart disease. In the treatment of unstable
angina, DSP improves non-symptomatic insufficient blow flow to
cardiac muscles. DSP can improve abnormal blood flow, lower blood
viscosity, relieve atherosclerosis, and prevent thrombosis more
efficiently than Isordil. It is an ideal drug for preventing and
treating coronary heart disease, angina and atherosclerosis. It can
end cardiac arrhythmia and prevent the reoccurrence of myocarditis
in patients with coronary heart disease, if it is used over a long
period of time.
[1024] Besides preventing damage from free radicals and
atherosclerosis, treating hyperlipidemia and high viscosity
syndrome, DSP can also lower blood viscosity and resistance in
blood vessels to regulate reverse LVH through capillary
circulation.
[1025] DSP can treat high blood pressure and efficiently regulate
blood pressure. It can also increase the sensitivity of insulin,
lower insulin level and improve the interior function of blood
vessels, which are important steps in treating high blood
pressure.
[1026] DSP can strengthen the primary immune system, increase the
immunosorbent ability of red blood cells, and improve primary
capillary circulation, which is helpful in acute myocardial
infarction and cerebral vessel lesion.
[1027] DSP can regulate vegetative nerve balance. It can control
high excitement in the sympathetic nerves to balance the vascular
nerve for the prevention of coronary heart disease.
[1028] DSP can efficiently treat hepatitis B, active liver
cirrhosis, chronic liver fibrosis and liver cirrhosis at the stage
of losing compensation.
[1029] DSP can treat diabetes and its companion diseases.
[1030] DSP can efficiently treat ocular nerve diseases and can be
applied widely to ocular diseases, such as central retinal artery
occlusion, hypertensive retinal arteriosclerosis, diatetic retinal
lesion, central plasm optic neuropathy, central permeation optic
neuropathy, ischemic optic neuropathy, optic neuritis, atrophy of
the optic nerve, etc.
[1031] DSP can treat dizziness caused by insufficient blood supply
to the cerebral artery, Meniere Disease, high blood pressure, and
coronary heart disease.
[1032] DSP can treat chronic and acute pulmonary heart disease, red
blood cell proliferation and bronchitis in children.
[1033] DSP can treat renal syndrome and its companion diseases.
[1034] DSP can treat hemicrania, chronic gastritis, fracture and
femofal head necrosis, ligament damage, broken bones, bone matrix
hyperplasia, plateau hypoxia and Alzheimer's Disease.
[1035] The following methods can further explain this invention in
different aspects. They are only used to explain this invention and
do not put on any restrictions on it.
EXAMPLE 1
[1036]
136 1. Prescription dosage Radix Salviae Miltiorrhizae 41.06 g
Radix Notoginseng 8.03 g borneol 0.46 g polyethylene glycol 6000 18
g Makes 1000 pills
[1037] 2. Extraction of Radix Salviae Miltiorrhizae and Radix
Notoginseng
[1038] Radix Salviae Miltiorrhizae and Radix Notoginseng are put
into extraction tank, added 5 times water as volume as above raw
materials, decocted for 2 hours, filtered, and the first filtrate
is got. The residue is added 4 times water as volume as above raw
materials, decocted for 1 hour, filtered, and then the filtrate is
mixed with the first filtrate. The mixed filtrate is concentrated
under decompressed conditions until the solution volume (L) to raw
materials weight (Kg) ratio is 0.9-1.1. 95% ethanol is gradually
poured in until the concentration of ethanol is 69-71%, settled for
12 hours, and filtered. The filtrate, in which ethanol is
evaporated, is concentrated to extract of the relative of
1.32-1.40.
[1039] 3. Preparation of Product
[1040] The above extract is mixed with borneol and polyethylene
glycol 6000. The mixture is heated to 85-90.degree. C., melted for
20-120 mins, and then transferred to a dropping machine at
85-90.degree. C. The melted mixture are dropped into the liquid
paraffin of which the temperature is at 7-8.degree. C. The dropping
pellets are taken out and the oil is removed.
[1041] 4. Characteristics of the Products
[1042] The product is a reddish brown-brownish black sphere with an
even size, smooth color, scent, and bitter taste. The weight is 25
mg 115%/pill, and the diameter is 3.34.+-.15% mm.
EXAMPLE 2
[1043]
137 1. Prescription dosage Radix Salviae Miltiorrhizae 31.12 g
Radix Notoginseng 9.21 g borneol 0.50 g polyethylene glycol 6000 20
g Makes 1000 pills
[1044] 2. The extraction of red sage root and notoginseng,
preparation and characteristics of the product are the same as
Example 1.
EXAMPLE 3
[1045]
138 1. Prescription dosage Radix Salviae Miltiorrhizae 59.36 g
Radix Notoginseng 6.38 g borneol 0.34 g polyethylene glycol 6000 21
g Makes 1000 pills
[1046] 2. The extraction of red sage root and notoginseng,
preparation and characteristics of the product are the same as
Example 1.
* * * * *